Glyphosate is widely used in agriculture for weed control; however, it may pollute water systems with its by-product, aminomethylphosphonic acid (AMPA). Therefore, a better understanding of the flows of glyphosate and AMPA from soils into rivers is required. We developed the spatially explicit MARINA-Pesticides model to estimate the annual inputs of glyphosate and AMPA into rivers, considering 10 crops in 10,226 sub-basins globally for 2020. Our model results show that, globally, 880 tonnes of glyphosate and 4,090 tonnes of AMPA entered rivers. This implies that 82 % of the river inputs were from AMPA, with glyphosate accounting for the remainder. Over half of AMPA and glyphosate in rivers globally originated from corn and soybean production; however, there were differences among sub-basins. Asian sub-basins accounted for over half of glyphosate in rivers globally, with the contribution from corn production being dominant. South American sub-basins accounted for approximately two-thirds of AMPA in rivers globally, originating largely from soybean production. Our findings constitute a reference for implementing and supporting effective control strategies to achieve Sustainable Development Goals 2 and 6 (food production and clean water, respectively) simultaneously in the future.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels.
METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB).
RESULTS: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction.
CONCLUSIONS: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

AMPA receptors are members of the glutamate receptor family and mediate a fast component of excitatory synaptic transmission at virtually all central synapses. Thus, their functional characteristics are a critical determinant of brain function. We evaluate intolerance of each GRIA gene to genetic variation using 3DMTR and report here the functional consequences of 52 missense variants in GRIA1-4 identified in patients with various neurological disorders. These variants produce changes in agonist EC50, response time course, desensitization, and/or receptor surface expression. We predict that these functional and localization changes will have important consequences for circuit function, and therefore likely contribute to the patients\' clinical phenotype. We evaluated the sensitivity of variant receptors to AMPAR-selective modulators including FDA-approved drugs to explore potential targeted therapeutic options.

Ketamine is a racemic mixture of equal amounts of R-ketamine and S-ketamine and is well known to anesthesiologists for its unique dissociative anesthetic properties. The pharmacological properties of ketamine, namely, its sympathetic excitation, mild respiratory depression, and potent analgesia, are still highly valued in its use as an anesthetic for some patients. In particular, since its advent, S-ketamine has been widely used as an anesthetic in many countries due to its increased affinity for NMDA receptors and its enhanced anesthetic and analgesic effects. However, the anesthetic and analgesic mechanisms of S-ketamine are not fully understood. In addition to antagonizing NMDA receptors, a variety of other receptors or channels may be involved, but there are no relevant mechanistic summaries in the literature. Therefore, the purpose of this paper is to review the mechanisms of action of S-ketamine on relevant receptors and systems in the body that result in its pharmacological properties, such as anesthesia and analgesia, with the aim of providing a reference for its clinical applications and research.

To explore the relationship between the proinflammatory factor high-mobility group box 1 (HMGB1) and glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the development of epilepsy.
Thalamic reticular nucleus (TRN) slices were treated with kainic acid (KA) to simulate seizures. Action potentials and spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded within TRN slices using whole-cell patch clamp techniques. The translocation of HMGB1 was detected by immunofluorescence. The HMGB1/TLR4 signaling pathway and its downstream inflammatory factors (IL-1β and NF-κB) were detected by RTPCR, Western blot and ELISA.
KA-evoked spikings were observed in TRN slices and blocked by perampanel. sIPSCs in the TRN were enhanced by KA and reduced by perampanel. The translocation of HMGB1 in the TRN was promoted by KA and inhibited by perampanel. The expression of the HMGB1/TLR4 signaling pathway was promoted by KA and suppressed by perampanel.
KA induced hyperexcitability activates the HMGB1/TLR4 pathway, which potentially leading to neuroinflammation in epilepsy.

With increasing concerns on the environment and human health, the degradation of glyphosate through the formation of less toxic intermediates is of great importance. Among the developed methods for the degradation of glyphosate, photodegradation is a clean and efficient strategy. In this work, we report a new photocatalyst by doping F ion on BiVO4 that can efficiently degrade glyphosate and reduce the toxic emissions of aminomethylphosphonic acid (AMPA) through the selective (P)-C-N cleavage in comparison of BiVO4 catalyst. The results demonstrate that the best suppression of AMPA formation was achieved by the catalyst of 0.3F@BiVO4 at pH = 9 (AMPA formation below 10%). In situ attenuated total reflectance Fourier transforms infrared (ATR-FTIR) spectroscopy indicates that the adsorption sites of glyphosate on BiVO4 and 0.3F@BiVO4 are altered due to the difference in electrostatic interactions. Such an absorption alteration leads to the preferential cleavage of the C-N bond on the N-C-P skeleton, thereby inhibiting the formation of toxic AMPA. These results improve our understanding of the photodegradation process of glyphosate catalyzed by BiVO4-based catalysts and pave a safe way for abiotic degradation of glyphosate.

Fast excitatory synaptic transmission in the CNS is mediated by the neurotransmitter glutamate, binding to and activating AMPA receptors (AMPARs). AMPARs are known to interact with auxiliary proteins that modulate their behavior. One such family of proteins is the transmembrane AMPAR-related proteins, known as TARPs. Little is known about the role of TARPs during development or about their function in nonmammalian organisms. Here, we report on the presence of TARP γ-4 in developing zebrafish. We find that zebrafish express 2 forms of TARP γ-4: γ-4a and γ-4b as early as 12 h post-fertilization. Sequence analysis shows that both γ-4a and γ-4b shows great level of variation particularly in the intracellular C-terminal domain compared to rat, mouse, and human γ-4. RT-qPCR showed a gradual increase in the expression of γ-4a throughout the first 5 days of development, whereas γ-4b levels were constant until day 5 when levels increased significantly. Knockdown of TARP γ-4a and γ-4b via either splice-blocking morpholinos or translation-blocking morpholinos resulted in embryos that exhibited deficits in C-start escape responses, showing reduced C-bend angles. Morphant larvae displayed reduced bouts of swimming. Whole-cell patch-clamp recordings of AMPAR-mediated currents from Mauthner cells showed a reduction in the frequency of mEPCs but no change in amplitude or kinetics. Together, these results suggest that γ-4a and γ-4b are required for proper neuronal development.

As the two most commonly used organophosphorus herbicides, glyphosate (Gly) and glufosinate-ammonium (Glu) have unique properties for weed control and algae removal in aquaculture. However, the occurrences and health risks of Gly and Glu in aquaculture ponds are rare known. This study aimed to investigate the occurrences of Gly, AMPA (primary metabolity of Gly) and Glu in surface water, sediment and aquatic products from the grass carp (ctenopharyngodon idella), crayfish (procambarus clarkii) and crab (eriocheir sinensis) ponds around Lake Honghu, the largest freshwater lake in Hubei province, China where aquaculture has become the local pillar industry. Three age groups (children, young adults, middle-aged and elderly) exposure to these compounds through edible aquatic products (muscle) consumption were also assessed by target hazard quotient (THQ) method. The results indicated that Gly, AMPA and Glu were widely occurred in surface water, sediment and organisms in the fish, crayfish and crab ponds. AMPA was more likely to accumulate in the intestine of aquatic products than Gly and Glu. According to the total THQ value (1.04＞1), muscle consumption of grass carp may pose potential risk to children.

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.

Agro-industries should adopt effective strategies to use agrochemicals such as glyphosate herbicides cautiously in order to protect public health. This entails careful testing and risk assessment of available choices, and also educating farmers and users with mitigation strategies in ecosystem protection and sustainable development. The key to success in this endeavour is using scientific research on biological pest control, organic farming and regulatory control, etc., for new developments in food production and safety, and for environmental protection. Education and research is of paramount importance for food and nutrition security in the shadow of climate change, and their consequences in food production and consumption safety and sustainability. This review, therefore, diagnoses on the use of glyphosate and the associated development of glyphosate-resistant weeds. It also deals with the risk assessment on human health of glyphosate formulations through environment and dietary exposures based on the impact of glyphosate and its metabolite AMPA-(aminomethyl)phosphonic acid-on water and food. All this to setup further conclusions and recommendations on the regulated use of glyphosate and how to mitigate the adverse effects.