Endogenous Release Research Articles

Endogenous phosphorus release from plateau lakes responds significantly to temperature variability over the last 50 years

The ecological environment of plateau lakes is very sensitive to temperature changes. Higher temperatures accelerate the cycling processes between lake sediments and water nutrients. Quantitatively investigating the influence mechanism of regional climate change and sediment phosphorus release over a long time series is difficult in revealing the causes of eutrophication in plateau lakes. This paper quantitatively reveals the long-term response mechanism of endogenous phosphorus release to temperature change in Dianchi, the largest plateau eutrophic lake in China, based on nearly 50 years of temperature and sediment phosphorus data from 1964 to 2013, and taking advantage of the Random Forest machine learning algorithm for deep processing of long time series and nonlinear relation. The results showed that: (1) Over the past 50 years, endogenous phosphorus release and temperature showed no trend for 22 years, followed by a consistent, significant increase in both after 1986. (2) Random Forest analysis showed that before the increase of temperature, the contribution to the phosphorus release was weak, while after the mutation, the contribution reached 52.6%, and typically was concentrated from March to August each year. (3) The response relationship between temperature and endogenous phosphorus release had non-linear variation with a threshold interval of 18.3 °C–19.2 °C. This research aims to explore the theoretical scientific knowledge of endogenous phosphorus release processes and complex mechanisms in plateau lakes under changing environments, and further explores the effects of long-term temperature variability on endogenous phosphorus loading in plateau lakes. That is, long-term temperature mutations can alter the internal cycling processes of sedimentary phosphorus by stimulating algal growth, which have a more drastic effect than short-term temperature variations.

Targeted Analysis of Mitochondrial Protein Conformations and Interactions by Endogenous ROS-Triggered Cross-Linker Release.

The study of in situ conformations and interactions of mitochondrial proteins plays a crucial role in understanding their biological functions. Current chemical cross-linking mass spectrometry (CX-MS) has difficulty in achieving in-depth analysis of mitochondrial proteins for cells without genetic modification. Herein, this work develops the reactive oxygen species (ROS)-responsive cross-linker delivery nanoparticles (R-CDNP) targeting mitochondria. R-CDNP contains mitochondria-targeting module triphenylphosphine, ROS-responsive module thioketal, loading module poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), and cross-linker module disuccinimidyl suberate (DSS). After targeting mitochondria, ROS-triggered cross-linker release improves the cross-linking coverage of mitochondria in situ. In total, this work identifies 2103 cross-linked sites of 572 mitochondrial proteins in HepG2 cells. 1718 intra-links reveal dynamic conformations involving chaperones with ATP-dependent conformation cycles, and 385 inter-links reveal dynamic interactions involving OXPHOS complexes and 27 pairs of possible potential interactions. These results signify that R-CDNP can achieve dynamic conformation and interaction analysis of mitochondrial proteins in living cells, thereby contributing to a better understanding of their biological functions.

Blocking endogenous phosphorus release in sediments by a hydrotalcite mixture synthesized with natural sepiolite and discarded cans

Pure hydrotalcite (LDH) materials prepared from chemical reagents have been investigated as solid-phase phosphorus (P) inactivation materials (SPIM) to manage endogenous P loading in sediments. However, the efficacy and mechanism of LDH mixtures prepared by natural minerals and solid wastes in controlling sediment P release are unclear. Therefore, a Ca/Mg-Al-LDH (CMA-LDH) material was synthesized using sepiolite and cans, and its efficacy, mechanism, and ecological impact in controlling sediment P release were investigated. CMA-LDH-p was prepared as a control material using pure chemical reagents. The CMA-LDH and CMA-LDH-p were both composed of hydrotalcite and hydrocalumite. The maximum P adsorption capacity of CMA-LDH was 123.01 mg/g, comparable to that of CMA-LDH-p. The adsorbed P by CMA-LDH was mostly in the stable P form, accounting for 87.2 % of the total P. The adsorption capacity and immobilization ability of CMA-LDH for P were superior to other reported LDH-based SPIM. Both the CMA-LDH addition and capping successfully blocked sediment P release under anaerobic conditions. Passivation of mobile P in the sediment and DGT-labile P in the interstitial water was critical to preventing sediment P release by the CMA-LDH addition. The CMA-LDH capping inhibited sediment P release through the effective adsorption of CMA-LDH on DGT-labile P at the sediment/overlying water interface. The CMA-LDH addition and capping affected the abundance of microbial communities associated with iron and sulfur cycling, which might affect the stability of endogenous P. These results confirmed that CMA-LDH addition and capping treatments were effective methods for managing sediment P loading.

Efficacy of P-sorbent material combined with aquatic plants in controlling nutrient release from urban lake sediment: Field investigation

The release of stored nutrients from sediments is thought to substantially affect water quality in urban lakes. To explore the efficiency of different in-situ remediation methods on controlling high internal urban lake sediments, 120 days of field-enclosure experiments were conducted to investigate the efficacy of P-sorbent materials combined with aquatic plants in controlling nutrient release from urban-lake sediments. The lanthanum-modified clay (LMC) effectively reduced sediment P release flux and could temporarily lead to a small increase in N concentration in the overlying water. In contrast, Vallisneria spiralis (V. spiralis) has a relatively weak effect on controlling nutrient release and can even cause an increase in P concentration. The combined restoration technique of V. spiralis + LMC can overcome the drawbacks of a single method, reduce the nutrient content in overlying water, and inhibit the sediment internal release. Relative to the control, the V. spiralis + LMC treatment reduced mobile P content by 52.5% and increased Ca-P content by 34.5%. The added lanthanum contained material can quickly bind the readily released P in sediment and porewater, transforming it into intert P over time. Submerged macrophytes can absorb active P in water and sediments and transport oxygen to sediments promoting denitrification and N removal. The combined restoration technique synergistically combines the high P sorption affinity of LMC and the substrate improvement effect of V. spiralis, thus realizing the long-term control of endogenous release in urban lakes. This approach holds great promise for restoring urban lakes with high endogenous nutrient loading.

Climate-driven decline in water level causes earlier onset of hypoxia in a subtropical reservoir

Hypoxia, especially in the bottom water, is occurring in deep and stratified reservoirs worldwide, threatening aquatic biodiversity, ecosystem functions and services. However, little is known about the timing of onset and ending of hypoxia, especially in subtropical reservoirs. Based on five-year (from April 2015 to January 2020) sampling of a subtropical monomictic deep reservoir (Tingxi Reservoir) in southeast China, we found the evidence of about 40 days earlier onset of hypolimnion hypoxia during low water level periods in dry years compared to wetter high water level years. We explored the effects of stratification and mixing conditions on hypoxia, cyanobacterial biomass, and nutrient dynamics; and revealed the physical and biochemical conditions that drove hypoxia. The results indicated that 1) The decline in water level increased the intensity of thermal stratification, resulting in 40 days earlier onset of hypolimnion hypoxia in dry years than in wet years; 2) The decline in water level expanded the extent of hypoxia by promoting nutrient accumulation and phytoplankton biomass growth; 3) Warmer climate and less precipitation (drought) significantly promoted the risk of hypoxic expansion and endogenous phosphorus release in subtropical reservoirs. We suggest that more attention needs to be paid to the early onset of hypoxia and its consequences on water quality in subtropical stratified reservoirs during low water level periods in a changing climate.

Mobilization of phosphorus in sediments of eutrophic lakes induced by elevated sulfate levels

Elevated sulfate levels in eutrophic lakes have been observed to induce the release of endogenous phosphorus. While previous studies have predominantly examined its impact on iron-bound phosphorus (FeP), the influence on organic phosphorus (OP), a crucial active phosphorus component in sediments, remains poorly understood. In this study, mesocosms were established with lactate supplementation and varying sulfate concentrations to explore sulfate reduction and its impacts on phosphorus mobilization in freshwater sediments. Lactate addition induced hypoxia and provided substrates, thereby stimulating sulfate reduction with a decline of sulfate levels, an increase of sulfide concentrations, and fluctuations of sulfate-reducing bacteria. Meanwhile, concentrations of total dissolved phosphorus and phosphate were dramatically promoted during lactate decomposition, with a higher sulfate concentration associated with greater phosphorus elevation, correlating with the decrease of total phosphorus in sediment. The increase in phosphorus of the overlying water was partly attributed to FeP release from the sediment, confirmed by a decrease in its sediment content. FeP release was ascribed to dissimilatory reduction of iron oxides or chemical reduction mediated by sulfides in anoxic sediments, leading to the desorption and subsequent release of phosphorus. Evidences included the proliferation of iron-reducing bacteria, a decrease in Fe(II) concentrations in sediment pore- water, and the continuous accumulation of solid iron sulfides in surface sediments. Furthermore, OP mineralization in sediment also contributed to the increase in phosphorus in water columns, confirmed by a reduction in its content and the abundance of fermentation bacteria in surface sediment. Notably, the decrease in OP content accounted for >80 % of the total phosphorus reduction in surface sediment in the end. Thus, sulfur cycling plays a critical role in iron and phosphorus cycling, significantly stimulating not only the mobilization of FeP but also OP in sediments, with OP mineralization potentially being the primary contributor to endogenous phosphorus release.

Balancing Placebo Use with Evidence-Based Treatments: The Placebo Effect in Clinical Practice and Research

The placebo effect has notable implications for clinical practice and research, demonstrating its ability to enhance therapeutic outcomes through psychological and physiological mechanisms. Evidence shows that placebos can impact treatment responses by influencing patients’ expectations and mental states, with mechanisms including neurobiological changes such as endogenous opioid release and brain activity alterations. However, their use raises ethical concerns, especially regarding patient trust and autonomy. Psychological factors like belief, expectation, and mindset play a significant role in placebo efficacy, affecting mental and physical health outcomes. In clinical settings, integrating placebo effects requires careful management to enhance patient care without replacing evidence-based treatments. Ethical integration involves boosting placebo responses transparently and maintaining adherence to ethical standards to prevent misuse, such as non-disclosure or substituting proven therapies, which can damage trust and patient autonomy. Future research aims to refine placebo mechanisms, including genetic factors and biomarkers—to personalize medicine and improve therapeutic efficacy—and evaluate the long-term effects of placebo responses on patient care. Placebos are essential in drug development and approval. Placebo-controlled trials help differentiate between active drug effects and psychological influences. However, ethical concerns, especially about withholding effective treatments, remain. Guidelines by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are crucial for upholding ethical standards in these trials. While the placebo effect offers valuable insights, its application must be managed with transparency and rigor to balance its benefits with high ethical standards in medical practice.

Stimulation Therapy to Induce Mothers: Protocol for a Multicenter Randomized Controlled Trial.

More than 1 million women have their labor induced in the United States each year, and synthetic oxytocin infusion is the most common method used. However, compared to spontaneous labor, medical induction is resource intensive, has increased obstetric risks, and is associated with less successful breastfeeding. In contrast to the endogenous oxytocin hormone, which is released in a pulsatile fashion in the brain, synthetic oxytocin is continuously infused intravenously, resulting in important limitations related to efficacy, safety, and cost. Akin to spontaneous labor contractions, infant suckling of the breast nipple is known to stimulate the pulsatile release of endogenous oxytocin from the posterior pituitary gland. Nipple stimulation therapy via an electric breast pump similarly stimulates endogenous oxytocin release and may be a favorable inpatient method for patients undergoing labor induction. This study aims to examine whether inpatient nipple stimulation therapy is an efficacious labor induction method that increases the likelihood of spontaneous vaginal delivery and sustained breastfeeding and determine whether it is a cost-effective approach. This is a multicenter, pragmatic, open-label, parallel-group randomized controlled trial of nulliparous patients with singleton gestations ≥36 weeks undergoing labor induction. This trial compares inpatient nipple stimulation therapy via an electric breast pump versus immediate synthetic oxytocin infusion without nipple stimulation. This trial including 988 nulliparas will provide adequate statistical power to detect clinically meaningful differences in delivery mode and breast milk as the sole source of nutrition for newborns at hospital discharge or 72 hours after birth. The project received pilot funding in 2021 and full funding in 2023. Enrollment for this study began in November 2021 at a single site, and as of May 2024, recruitment is underway at 3 study sites. It is anticipated that enrollment will be completed by late 2026. Successful completion of this trial will provide rigorous data to determine whether inpatient nipple stimulation therapy with an electric breast pump can improve the way we induce labor and positively impact breastfeeding success and early infant nutrition through lactation. ClinicalTrials.gov NCT05079841; https://clinicaltrials.gov/study/NCT05079841. DERR1-10.2196/63463.

Exogenous paths regulate electron transfer enhancing sediment phosphorus immobilization

The lack of electron acceptors in anaerobic sediments leads to endogenous phosphorus release and low removal efficiency of organic pollutants. This study introduced electrodes and iron oxides into sediments to construct electron network transport chains to supplement electron acceptors. The sediment total organic carbon (TOC) removal efficiencies of closed-circuit (CC) and closed-circuit with Fe addition (CC-Fe) were estimated to be 1.4 and 1.7 times of the control. Unlike the fluctuation of phosphorus in the overlying water of the controls, the CC-Fe was stabled at 0.04–0.08 mg/L during the 84-d operation. The phosphorus in interstitial water of CC-Fe was 30 % less than in control, whereas in sediment, the redox sensitive phosphorus was increased by 14 %, indicating phosphorus was preferred to fix into sediments rather than interstitial water. This is important to reduce the risk of endogenous phosphorus returning to the overlying water. Microbial community analysis showed that the multiplication of Fonticella in CC-Fe (20 %) was 1.8-fold of control (11 %) which improved the TOC removal efficiency. While electroactive microorganisms accumulated near the electrode reduced the abundance of Fe-reducing bacteria, such as Desulfitobacterium (2.4 %), leading to better phosphorus fixation. These findings suggest a strategy for the efficient bioremediation of endogenous pollution in water, with broader implications for regulating electron transport paths and element cycles in aquatic environments.

Postsynaptic GABAB-receptor mediated currents in diverse dentate gyrus interneuron types.

The processing of rich synaptic information in the dentate gyrus (DG) relies on a diverse population of inhibitory GABAergic interneurons to regulate cellular and circuit activity, in a layer-specific manner. Metabotropic GABAB-receptors (GABABRs) provide powerful inhibition to the DG circuit, on timescales consistent with behavior and learning, but their role in controlling the activity of interneurons is poorly understood with respect to identified cell types. We hypothesize that GABABRs display cell type-specific heterogeneity in signaling strength, which will have direct ramifications for signal processing in DG networks. To test this, we perform in vitro whole-cell patch-clamp recordings from identified DG principal cells and interneurons, followed by GABABR pharmacology, photolysis of caged GABA, and extracellular stimulation of endogenous GABA release to classify the cell type-specific inhibitory potential. Based on our previous classification of DG interneurons, we show that postsynaptic GABABR-mediated currents are present on all interneuron types albeit at different amplitudes, dependent largely on soma location and synaptic targets. GABABRs were coupled to inwardly-rectifying K+ channels that strongly reduced the excitability of those interneurons where large currents were observed. These data provide a systematic characterization of GABABR signaling in the rat DG to provide greater insight into circuit dynamics.

High-Throughput Evolution of Near-Infrared Oxytocin Nanosensors

Neuropeptide oxytocin is known for its crucial regulatory role in various social behaviors, yet our understanding of its function in the brain remains incomplete. There is a demonstrable need for an imaging probe with the requisite specificity and resolution to image endogenous oxytocin signaling. Here, we leverage an evolution-based molecular recognition platform called Systematic Evolution of Ligands by Exponential Enrichment on Carbon Nanotubes (SELEC).1 With an initial library of over 1010 DNA sequences, we conducted six iterative rounds of competitive DNA-SWNCT binding in the presence and absence of oxytocin, respectively termed experimental and control SELEC, followed by adsorbed DNA isolation and enzymatic amplification to prepare the aptamer library for the subsequent round. Deep sequencing analysis and oxytocin sensitivity screening of the most enriched constructs per round revealed that oxytocin incubation enhanced the appearance of highly responsive DNA-SWCNT; only top nanosensors from SELEC experimental rounds 5 and 6 demonstrated a normalized ΔF/F0 greater than 60% in response to 100 µM oxytocin. Furthermore, the most oxytocin-sensitive aptamer was identified as E6#4, the 4th most-enriched sequence from the 6th experimental round. We briefly discuss how machine learning approaches can mine sequencing data from our SELEC experimental rounds to identify top-performing oxytocin nanosensors.Lastly, we characterize the top nanosensor candidates for sensitivity, selectivity, and reversibility, prior to demonstrating their use to image endogenous oxytocin release in acute brain slices. Our results indicate SELEC can serve as a general approach to evolving molecular recognition and developing imaging probes for complex targets such as oxytocin.1. Jeong, S.; Yang, D.; Beyene, A. G.; Travis, J.; Bonis-O’donnell, D.; Gest, A. M. M.; Navarro, N.; Sun, X.; Landry, M. P. High-Throughput Evolution of near-Infrared Serotonin Nanosensors; 2019; Vol. 5, pp 3771–3789. Figure 1

Control of Dopamine Signal in High-Order Receptor Complex on Striatal Astrocytes.

The receptor-receptor interaction (RRI) of G protein-coupled receptors (GPCRs) leads to new functional entities that are conceptually distinct from the simple addition of signals mediated by the activation of the receptors that form the heteromers. Focusing on astrocytes, there is evidence for the existence of inhibitory and facilitatory RRIs, including the heteromers formed by the adenosine A2A and the dopamine D2 receptors, by A2A and the oxytocin receptor (OTR), and the D2-OTR heteromers. The possible involvement of these receptors in mosaicism has never been investigated in striatal astrocytes. By biophysical and functional approaches, we focused our attention on the existence of an A2A-D2-OTR high-order receptor complex and its role in modulating cytosolic calcium levels and endogenous glutamate release, when striatal astrocyte processes were stimulated with 4-aminopyridine. Functional data indicate a permissive role of OTR on dopamine signaling in the regulation of the glutamatergic transmission, and an inhibitory control mediated by A2A on both the D2-mediated signaling and on the OTR-facilitating effect on D2. Imaging biochemical and bioinformatic evidence confirmed the existence of the A2A-D2-OTR complex and its ternary structure in the membrane. In conclusion, the D2 receptor appears to be a hotspot in the control of the glutamate release from the astrocytic processes and may contribute to the regulation and integration of different neurotransmitter-mediated signaling in the striatum by the A2A-D2-OTR heterotrimers. Considering the possible selectivity of allosteric interventions on GPCRs organized as receptor mosaics, A2A-D2-OTR heterotrimers may offer selective pharmacological targets in neuropsychiatric disorders and neurodegenerative diseases.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Nano-photosensitizers with gallic acid-involved Fe–O–Cu “electronic storage station” bridging ligand-to-metal charge transfer for efficient catalytic theranostics

NH2-MIL-88B (Fe) (MOF) is a promising photocatalytic material for antitumor therapy because of its distinctive electronic structure. However, inadequate separation of photo-generated electrons and slow reaction rate in low/high-valence iron (Fe) cycles limit their clinical application. In the present study, “electronic storage station” as a ligand-to-metal charge transfer bridge bond was constructed to inhibit recombination of electron/hole under 650 nm laser irradiation. Cupric (Cu) ions and gallic acid (GA) were self-assembled into a MOF (denoted as CGMOF) to create an FeO(GA)Cu bridge bond. GA, characterized by robust electron delocalization and abundant electron-donating groups, significantly enhances electron transfer efficiency for photodynamic therapy (PDT). CGMOF can respond to endogenous glutathione and release cuprous ions, accelerating the iron ion/ferrous ion cycles for chemodynamic therapy (CDT). The released Fe species can serve as T2-weighted magnetic resonance imaging contrast. Extended X-ray absorption fine structure spectra confirmed the presence of GA-containing FeOCu bonds in CGMOF. Furthermore, a series of photo-electrochemical tests confirmed that the formation of FeO(GA)Cu bond prominently elevated the redox capacity and increased the carrier density of CGMOF by 2.74-fold compared to that of MOF. In addition, cinnamaldehyde was grafted onto CGMOF for tumor-responsive hydrogen peroxide self-supply. Concurrently, hyaluronic acid was surface-modified to achieve the targeted delivery of nano-photosensitizers. In summary, this study presents an innovative approach for engineering Fe-based metal–organic frameworks for synergetic PDT/CDT applications.

Oxytocin and cortisol concentrations in urine and saliva in response to physical exercise in humans

BackgroundWhile peripheral markers of endogenous oxytocin and glucocorticoid release are widely employed in psychological and behavioural research, there remains uncertainty regarding the effectiveness of saliva and urine samples in accurately capturing fluctuating hormone levels in response to relevant stimuli. In addition, it is unclear whether and under which conditions, urinary concentrations correlate with salivary levels of oxytocin and cortisol. MethodsIn the present study, two groups of healthy adult male and female participants (N=43) provided heart rate, saliva, and urine samples before and after exercising at different durations and intensities (3 ×10 min of running vs. 60 min of running). Effects of age, gender, cycle phase, and previous running experience were considered in the statistical analyses. Concentrations of oxytocin and cortisol were analysed in both saliva, and urine using validated assays. ResultsRunners of both groups had significantly increased oxytocin concentrations in urine and saliva after running than before. Oxytocin in saliva was elevated after 10 min and peaked after 30 min of running. Only participants of the long-running group showed an increase in urinary cortisol concentrations following exercise (and only after 90 min of stimulus onset), and neither group had a significant increase in salivary cortisol levels. Oxytocin rise in urine and saliva from basal to post-run was strongly and significantly correlated, as was cortisol rise from basal to post-rest, but no correlations between absolute hormone concentrations were found for oxytocin. ConclusionsOur results show that both urine and saliva are useful body fluids that can provide meaningful results when measuring oxytocin and cortisol concentrations after a physical stimulus. While temporal resolution may be better with salivary sampling as higher sampling frequency is possible, signal strength and robustness were better in urinary samples. Importantly, we report a strong correlation between the magnitude of change in oxytocin and cortisol concentrations in urine and saliva following physical exercise, but no correlations between absolute oxytocin concentrations in the two substrates.

Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.

Irritability, a state of excessive reactivity to negative emotional stimuli, is common in individuals with autism spectrum disorder (ASD). Although it has a significant negative impact of patients' disease severity and quality of life, the neural mechanisms underlying irritability in ASD remain largely unclear. We have previously demonstrated that male mice lacking the Coiled-coil and C2 domain containing 1a (Cc2d1a) in forebrain excitatory neurons recapitulate numerous ASD-like behavioral phenotypes, including impaired social behaviors and pronounced repetitive behaviors. Here, using the bottle-brush test (BBT) to trigger and evaluate aggressive and defensive responses, we show that Cc2d1a deletion increases irritability-like behavior in male but not female mice, which is correlated with reduced number of oxytocin (OXT)-expressing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Intranasal OXT administration or chemogenetic activation of OXT neurons in the PVN rescues irritability-like behavior in Cc2d1a conditional knockout (cKO) mice. Administration of a selective melanocortin receptor 4 agonist, RO27-3225, which potentiates endogenous OXT release, also alleviates irritability-like behavior in Cc2d1a cKO mice, an effect blocked by a specific OXT receptor antagonist, L-368,899. We additionally identify a projection connecting the posterior ventral segment of the medial amygdala (MeApv) and ventromedial nucleus of the ventromedial hypothalamus (VMHvl) for governing irritability-like behavior during the BBT. Chemogenetic suppression of the MeApv-VMHvl pathway alleviates irritability-like behavior in Cc2d1a cKO mice. Together, our study uncovers dysregulation of OXT system in irritability-like behavior in Cc2d1a cKO mice during the BBT and provide translatable insights into the development of OXT-based therapeutics for clinical interventions.

Unlocking opioid neuropeptide dynamics with genetically encoded biosensors

Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

Spatial heterogeneity, sediment-water exchange, and diffusion mechanisms of organophosphate esters from river to coastal aquatic system in a typical economic circle of northern China

Organophosphate esters (OPEs) have proven to be pervasive in aquatic environments globally. However, understanding their partitioning behavior and mechanisms at the sediment-water interface remains limited. This study elucidated the spatial heterogeneity, interfacial exchange, and diffusion mechanisms of 14 OPEs (∑14OPEs) from river to coastal aquatic system. The transport tendencies of OPEs at the sediment-water interface were quantitatively assessed using fugacity methods. The total ∑14OPEs concentrations in water and sediments ranged from 154 ng/L to 528 ng/L and 2.41 ng/g dry weight (dw) to 230 ng/g dw, respectively. This result indicated a descending spatial tendency with moderate variability. OPE distribution was primarily influenced by temperature, pH, and dissolved oxygen levels. As the carbon atom number increased, alkyl and chlorinated OPEs transitioned from diffusion towards the aqueous phase to equilibrium. In contrast, aryl OPEs and triphenylphosphine oxide, which had equivalent carbon atom counts, maintained equilibrium throughout. Diffusion trends of individual OPE congener at the sediment-water interface varied at the same total organic carbon contents (foc). As the foc increased, the fugacity fraction values for all OPE homologs showed a declining trend. The distinct molecular structure of each OPE monomer might lead to unique diffusive behaviors at the sediment-water interface. Higher soot carbon content had a more pronounced effect on the distribution patterns of OPEs. The sediment-water distribution of OPEs was primarily influenced by total organic carbon, sediment particle size, dry density, and moisture content. OPEs displayed the highest sensitivity to fluctuations in ammonium and dissolved organic carbon. This study holds significant scientific and theoretical implications for elucidating the interfacial transport and driving forces of OPEs and comprehending their fate and endogenous release in aquatic ecosystems.

New insight into enhanced carbon recovery from anaerobic fermentation of waste activated sludge with cation exchange resin coupled with NaCl pretreatment

Carbon recovery from waste activated sludge has been attracting considerable attention. However, the migration and transformation patterns of carbon sources between the phases have rarely been reported. In this study, a novel strategy using cation exchange resin (CER) coupled with sodium chloride (NaCl) to enhance carbon recovery through anaerobic fermentation (AF) was proposed. The results demonstrated that CER coupled with NaCl destroyed OH and CO stretching in amide I while promoting the formation of β-sheet and random coil structures, leading to sludge disintegration. This significantly improved the kinetics of endogenous carbon release, resulting in the release of 1146.33 mg/L of carbon from the solid sludge into the liquid phase. Approximately 75.61 % of the initial carbon source was bio-transformed into short-chain fatty acids. Correspondingly, carbon recovery was significantly increased up to 852.23 mg C/L, 4.57 times that of the control. Mechanism exploration revealed that carbon source recovery was significantly elevated by the synergistic effect of CER and NaCl. CER effectively removed high-valence cations from extracellular polymeric substance (EPS), weakening its bridging and adsorption-electro neutralization capabilities, promoting protein deflocculation, and triggering EPS disruption to release extracellular carbon sources. NaCl disrupted the ionic strength and distribution inside and outside microbial cells, creating an osmotic pressure difference that resulted in cell plasmolysis and lysis, ultimately inducing the release of intracellular carbon sources. Economic and carbon emission reduction benefit analyses verified that the CER coupled with NaCl pretreatment is a cost-effective sludge treatment strategy. This study illustrates the carbon source migration and transformation pathways in the CER coupled with NaCl-assisted AF process, providing guidance for sustainable sludge management.

Exploratory study of associations between monetary reward anticipation brain responses and mu-opioid signalling in alcohol dependence, gambling disorder and healthy controls

Alcohol dependence (AD) and gambling disorder (GD) are common addiction disorders with significant physical and mental health consequences. AD and GD are associated with dysregulated responses to reward which could be due to a common mechanism of dysregulated endogenous opioid signalling. We explored associations between reward anticipation responses, using the Monetary Incentive Delay (MID) functional magnetic resonance imaging (fMRI) task, and mu-opioid receptor (MOR) availability and endogenous opioid release capacity using [11C]carfentanil positron emission tomography (PET), in 13 AD, 15 GD and 14 heathy control (HC) participants. We also examined differences in MID task reward anticipation responses between AD, GD and HC participants. These were secondary exploratory analysis of data collected to examine differences in MOR PET in addiction. We did not find significant differences in MID win > neutral anticipation BOLD responses compared between participant groups in a priori ROIs (ventral striatum, putamen, caudate) or whole brain analyses. We found no significant correlations between MID win > neutral anticipation BOLD responses and [11C]carfentanil PET measures, except for limited negative correlations between putamen MOR availability and MID win > neutral anticipation BOLD response in AD participants. Previous research has suggested a limited role of endogenous opioid signalling on MID task reward anticipation responses in AD and HCs as these responses are not modulated by opioid receptor blockade and this may explain our lack of significant correlations in HC and AD or GD participants. Our results, particularly the lack of differences in MID win > neutral anticipation BOLD responses across participants groups, may be limited due to only including AD or GD participants who are abstinent or in active treatment.