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Background and purpose Methods Results Conclusions Neuropeptide Y (NPY) has been reported to be involved in the pathophysiology of several cardiovascular disease processes and might contribute to the incidence of stroke, but the prognostic utility of circulating NPY after acute ischaemic stroke is unclear. This study aimed to prospectively examine the association between plasma NPY levels and adverse clinical outcomes after acute ischaemic stroke.Plasma NPY levels were measured in 3250 patients (2066 men and 1184 women) from the China Antihypertensive Trial in Acute Ischaemic Stroke. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 12 months after stroke onset, and secondary outcomes included major disability, death and cardiovascular events.During the 12‐month follow‐up, 702 participants (21.6%) experienced major disability or died. After multivariable adjustment, odds ratio (95% confidence interval) for the highest quartile of NPY was 1.56 (1.19–2.04) for the primary outcome, compared to the lowest quartile. Each standard deviation (0.27 ng/mL) higher log‐transformed NPY was associated with an odds ratio (95% confidence interval) of 1.18 (1.07–1.30) for the primary outcome, 1.28 (1.15–1.42) for major disability. The addition of NPY to a conventional risk factors model improved risk prediction of the composite outcome of death and major disability (category‐free net reclassification index 8.82%, p = 0.040; integrated discrimination improvement 0.38%, p = 0.011).Elevated plasma NPY levels in the acute phase of ischaemic stroke were associated with increased risk of poor clinical outcomes after ischaemic stroke, suggesting that plasma NPY may be a potential prognostic biomarker for ischaemic stroke. [ABSTRACT FROM AUTHOR]

Introduction: Light is the primary source of energy and regulates seasonal changes in physiology and behavior. The role of photoperiod has been much investigated in several bird species, but the role of illumination in seasonal adaptations of passerine finches is less understood. We, therefore, investigated the effects of photoperiod and illuminance on migratory physiology in a Palearctic-Indian migratory finch, redheaded bunting (Emberiza bruncieps). Methods: Photosensitive buntings maintained under short days (8L:16D) were divided into three groups receiving 5, 25, and 100 lux of white daytime illuminance, respectively. Thereafter, using photoperiodic manipulation three life history states, i.e., nonmigratory (NM), premigratory (PM), and migratory (MIG) states were induced in the buntings. The birds in the MIG state were consecutively perfused after seven nights of Zugunruhe (nighttime migratory restlessness) for neuropeptide Y (NPY)-immunohistochemistry, which is involved in a wide range of functions including energy homeostasis, vision, and fat deposition in birds. Results: We found differential effects of illuminance on locomotor activity and physiology. Photostimulated birds showed intense nighttime activity in the MIG state. We observed premigratory hyperphagia in the birds, with increased food intake in the 100 lux group, which was reflected in the body mass gain in the MIG state. NPY expression on the periphery of the nucleus rotundus suggests its potential role in visual acuity, where the NPY-cell count significantly decreased under 25 lux illumination. Conclusion: We demonstrate that migrating birds may also experience physiological effects from changes in daytime illumination. We observed illuminance-dependent variations in the quantity of food consumed by the birds. It indicates that the illuminance may also impact the encephalic centers that control food intake. [ABSTRACT FROM AUTHOR]

Background: The pivotal responsibility of GABAergic interneurons is inhibitory neurotransmission; in this way, their significance lies in regulating the maintenance of excitation/inhibition (E/I) balance in cortical circuits. An abundance of glucocorticoids (GCs) exposure results in a disorder of GABAergic interneurons in the prefrontal cortex (PFC); the relationship between this status and an enhanced vulnerability to neuropsychiatric ailments, like depression and anxiety, has been identified, but this connection is still poorly understood because systematic and comprehensive research is lacking. Here, we aim to investigate the impact of dexamethasone (DEX, a GC receptor agonist) on GABAergic interneurons in the PFC of eight-week-old adult male mice. Methods: A double-blind study was conducted where thirty-two mice were treated subcutaneously either saline or DEX (0.2 mg/10 ml per kg of body weight) dissolved in saline daily for 21 days. Weight measurements were taken at five-day intervals to assess the emotional changes in mice as well as the response to DEX treatment. Following the 21-day regimen of DEX injections, mice underwent examinations for depression/anxiety-like behaviours and GABAergic marker expression in PFC. Results: In a depression/anxiety model generated by chronic DEX treatment, we found that our DEX procedure did trigger depression/anxiety-like behaviors in mice. Furthermore, DEX treatment reduced the expression levels of a GABAsynthesizing enzyme (GAD67), Reelin, calcium-binding proteins (parvalbumin and calretinin) and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y and vasoactive intestinal peptide) in the PFC were reduced after 21 days of DEX treatment; these reductions were accompanied by decreases in brain size and cerebral cortex thickness. Conclusion: Our results indicate that a reduction in the number of GABAergic interneurons may result in deficiencies in cortical inhibitory neurotransmission, potentially causing an E/I imbalance in the PFC; this insight suggests a potential breakthrough strategy for the treatment of depression and anxiety. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions Pharmacotherapeutic options for obesity treatment include glucagon‐like peptide‐1 receptor (GLP‐1R) agonists, for example, liraglutide. However, an unmet need remains, particularly in patients with a high body mass index (BMI), as GLP‐1R agonists are associated with gastrointestinal adverse events (AEs) and some patients do not respond to treatment. Neuropeptide Y (NPY) and peptide YY bind G‐protein‐coupled Y receptors and represent attractive targets for modulating bodyweight.This first‐in‐human, three‐part, partially blinded phase I study (NCT04903509) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of the peptidic NPY2R agonist BI 1820237, with/without low‐dose liraglutide: part 1 (participants randomized to receive BI 1820237: 0.075–2.4 mg or placebo), part 2 (BI 1820237: 1.2 mg or placebo) and part 3 (BI 1820237: 0.025–1.2 mg + liraglutide 0.6 mg or placebo + liraglutide 0.6 mg). Primary endpoint is the proportion of participants with drug‐related AEs. Secondary endpoints are tolerability, PK and PD.In total, 95 otherwise healthy men with increased BMI (25.0–34.9 kg/m2) were randomized. Drug‐related AEs, mainly gastrointestinal events, were reported by 39.0% of participants (n = 23) in parts 1 + 2 and 30.6% of participants (n = 11) in part 3; one drug‐related AE (11.1%, part 3) was reported in a participant receiving placebo with liraglutide. Post‐dose paracetamol PK suggested that BI 1820237 and low‐dose liraglutide exhibited additive effects on gastric emptying.BI 1820237 treatment was associated with transient nausea and vomiting at higher doses. No differences in tolerability were observed when combined with liraglutide; effects on gastric emptying appeared additive. [ABSTRACT FROM AUTHOR]

Neuropeptide cocaine‐ and amphetamine‐regulated transcript (CART) is widely expressed in the brains of teleosts, amphibians, birds, and mammals and has emerged as a conserved regulator of energy balance across these vertebrate phyla. However, as yet, there is no information on CART in the reptilian brain. We characterized the cDNA encoding CART and mapped CART‐containing elements in the brain of gecko, Hemidactylus leschenaultii (hl) using a specific anti‐CART antiserum. We report a 683‐bp hlcart transcript containing a 336‐bp open reading frame, which encodes a putative 111‐amino acid hl‐preproCART. The 89‐amino acid hl‐proCART generated from hl‐preproCART produced two putative bioactive hl‐CART‐peptides. These bioactive CART‐peptides were > 93% similar with those in rats/humans. Although reverse transcription‐polymerase chain reaction (RT‐PCR) detected hlcart‐transcript in the brain, CART‐containing neurons/fibers were widely distributed in the telencephalon, diencephalon, mesencephalon, rhombencephalon, spinal cord, and retina. The mitral cells in olfactory bulb, neurons in the paraventricular, periventricular, arcuate (Arc), Edinger–Westphal, and brainstem nuclei were intensely CART‐positive. In view of antagonistic roles of neuropeptide Y (NPY) and CART in energy balance in the framework of mammalian hypothalamus, we probed CART–NPY interaction in the hypothalamus of H. leschenaultii. Double immunofluorescence showed a dense NPY‐innervation of Arc CART neurons. Ex vivo hypothalamic slices treated with NPY/NPY‐Y1‐receptor agonist significantly reduced hlcart‐mRNA levels in the Arc‐containing tissues and CART‐ir in the dorsal‐Arc. However, CART‐ir in ventral‐Arc was unaffected. NPY via Y1‐receptors may regulate energy balance by inhibiting dArc CART neurons. This study on CART in a reptilian brain fills the current void in literature and underscores the conserved feature of the neuropeptide across the entire vertebrate phyla. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heterodimer peptides targeting more than one receptor can be advantageous, as tumors can simultaneously express more than one receptor type. For human breast cancer, a promising biological target is tumor angiogenesis through αvβ3 integrin expression. Another promising target is Neuropeptide Y receptors, considering Y1R is overexpressed in 90% of human breast tumors. This article details the development and preclinical evaluation, both in vitro and in vivo, of a novel heterodimer peptide dual-receptor-targeting probe, [99mTc]HYNIC-cRGDfk-NPY, designed for imaging breast tumors. Methods: Female BALB/c healthy mice were used to perform biodistrubution studies and female SCID mice were subcutaneously injected with MCF-7 and MDA-MB-231 tumor cells. [99mTc]HYNIC-cRGDfk-NPY was intravenously administered to the mice, followed by ex vivo biodistribution studies and small-animal SPECT/CT imaging. Nonspecific tracer uptake in both models was determined by coinjecting an excess of unlabeled HYNIC-cRGDfk-NPY (100 µg) along with the radiolabeled tracer. Results: Imaging and biodistribution data demonstrate good uptake to estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) tumor models. The in vivo tumor uptakes of radiolabeled conjugate were 9.30 ± 3.25% and 4.93 ± 1.01% for MCF-7 and MDA-MB231, respectively. The tumor/muscle ratios were 5.65 ± 0.94 for the MCF-7 model and 7.78 ± 3.20 for MDA-MB231. Conclusions: [99mTc]HYNIC-cRGDfk-NPY demonstrated rapid blood clearance, renal excretion, and in vivo tumor uptake, highlighting its potential as a tumor imaging agent. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) is a 36-amino acid peptide that is widely expressed throughout the limbic system. Recent evidence has highlighted NPY as a marker of resilience to posttraumatic psychopathology, which may be due to its association with neural regions involved with emotion regulation. This study examined whether plasma NPY levels moderated the relationship between emotion regulation and psychopathology in a sample of adult survivors of childhood interpersonal trauma, a population known to be at high risk for psychopathology. Adults exposed to an interpersonal criterion A trauma during childhood (N = 54) were recruited from an urban population at a midwestern medical center and completed a baseline study visit as part of a larger clinical trial. Participants gave a blood sample in order to assess circulating levels of NPY and answered questions related to emotion regulation and mood-related pathology. Results of a moderated multiple regression showed that the overall model was significant R 2 = 0.26, F (5, 48) = 3.46, p <.01. Difficulties in emotion regulation was significantly predictive of psychopathology (unstandardized B = 0.032, p <.01), and this relationship was significantly moderated by levels of NPY (unstandardized B = −0.001, p <.05) such that the relationship between emotion regulation and psychopathology was weaker for those with higher levels of NPY. Results suggest that higher levels of NPY may lessen the association between emotion regulation and posttraumatic psychopathology in survivors of childhood interpersonal trauma. Further investigation of the contribution of NPY to psychopathology in this population is warranted. 02279290. • We assessed adult survivors of childhood interpersonal trauma. • Blood samples and self-report questionnaires were collected. • Higher neuropeptide-Y (NPY) was associated with better emotion regulation. • Better emotion regulation was associated with reduced mood-related symptoms. • NPY moderated the relationship between emotion regulation and mood-related symptoms. [ABSTRACT FROM AUTHOR]

Background: Adolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies. Methods: Male and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus. Results: The main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females. Conclusions: This study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders. Plain English summary: Experiencing stress and consuming alcohol during the teenage years can significantly raise the risk of developing mental health problems later in life. These risks can vary between males and females, making it important to understand how each sex is differently affected. This study investigated how exposure to acute stress and intermittent alcohol use during adolescence impacts male and female rats as they reach young adulthood. Our research involved first measuring the levels of stress hormones in the blood to see how these early experiences influenced the body's stress response. Following this, we closely examined changes in the expression of specific genes within two critical brain regions: the amygdala and the hypothalamus. These regions play a crucial role in controlling emotional states, managing stress, and regulating behaviors related to addiction. The results of the study revealed that both stress and alcohol exposure during adolescence led to lasting alterations in stress hormone levels and changes in the expression of genes within the brain. Importantly, these effects were not the same for males and females, highlighting the presence of sex-specific differences. Understanding these differences can guide the development of more effective treatments, ultimately improving mental health outcomes for both males and females. Highlights: Acute stress led to decreased BAC levels in male rats after the final alcohol administration in a binge drinking model, without effects on female rats. Stressed female rats showed elevated ACTH levels compared to non-stressed females, while interactions between stress and alcohol produced sex-specific effects on CORT levels. Adolescent alcohol increased Crh gene expression in the amygdala in both sexes, with additional sex-dependent alterations in related receptor genes in the amygdala and hypothalamus. Stress and alcohol had sexually dimorphic effects on Npy gene expression in the amygdala, lowering levels in stressed males but increasing them in stressed females. The expression of opioid receptor genes, such as Oprm1 and Oprd1, was significantly altered by adolescent stress and alcohol exposure, with sex-specific patterns in the amygdala and hypothalamus. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Obesity is a non‐communicable complex disease that is the fifth leading cause of death worldwide. According to a novel viewpoint, the brain plays a significant role in the central regulation of satiety and energy homeostasis. Because of its rich nutritional profile and versatile uses, oat (Avena sativa) is one of the most popular functional foods recommended by many nutritionists. The anti‐obesity effect of oat was hypothesized, focusing on the brain as the target organ. In the current study, the interplay between brain biomarkers, obesity, and its related complications was evaluated in diet‐induced obese rats for 25 weeks, in which 60 adult male white albino Wistar rats were divided into three control and seven treatment groups given oat extracts in a dose‐dependent manner.Oat significantly improved obesity‐related metabolic complications. In terms of brain function, oat significantly increased dopaminergic signaling, brain‐derived neurotrophic factor levels, vaspin, irisin, and uncoupling protein‐1 brain levels, while decreasing the expression of agouti‐related peptide and neuropeptide Y (P‐value < 0.05).The current study proposes oat supplementation as a new conceptual framework with numerous implications for hedonic and homeostatic mechanisms that control satiety. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The hormone Neuropeptide Y (NPY) plays critical roles in feeding, satiety, obesity, and weight control. However, its complex peptide structure has hindered the development of fast and biocompatible detection methods. Previous studies utilizing electrochemical techniques with carbon fiber microelectrodes (CFMEs) have targeted the oxidation of amino acid residues like tyrosine to measure peptides. Here, we employ the modified sawhorse waveform (MSW) to enable voltammetric identification of NPY through tyrosine oxidation. Use of MSW improves NPY detection sensitivity and selectivity by reducing interference from catecholamines like dopamine, serotonin, and others compared to the traditional triangle waveform. The technique utilizes a holding potential of −0.2 V and a switching potential of 1.2 V that effectively etches and renews the CFME surface to simultaneously detect NPY and other monoamines with a sensitivity of 5.8 ± 0.94 nA/µM (n = 5). Furthermore, we observed adsorption-controlled, subsecond NPY measurements with CFMEs and MSW. The effective identification of exogenously applied NPY in biological fluids demonstrates the feasibility of this methodology for in vivo and ex vivo studies. These results highlight the potential of MSW voltammetry to enable fast, biocompatible NPY quantification to further elucidate its physiological roles. [ABSTRACT FROM AUTHOR]

Metabotropic glutamate receptor 4 (mGluR4) is widely regarded as an umami receptor activated by L-glutamate to exert essential functions. Numerous studies have shown that umami receptors participate in food intake regulation. However, little is known about mGluR4's role in mediating food ingestion and its possible molecular mechanism. Mandarin fish, a typical carnivorous fish, is sensitive to umami substances and is a promising vertebrate model organism for studying the umami receptor. In this study, we identified the mGluR4 gene and conducted evolutionary analyses from diverse fish species with different feeding habits. mGluR4 of mandarin fish was cloned and functionally expressed to investigate the effects of L-glutamate on mGluR4. We further explored whether the signal pathway mGluR4-Ca2+-ERK1/2 participates in the process in mandarin fish brain cells. The results suggest that L-glutamate could regulate Neuropeptide Y (Npy) via the mGluR4-Ca2+-ERK1/2 signaling pathway in mandarin fish. Our findings unveil the role of mGluR4 in feeding decisions and its possible molecular mechanisms in carnivorous fishes. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY. [ABSTRACT FROM AUTHOR]

Background: Addressing the shortage of high-quality protein resources, this study was conducted to investigate the effects of replacing soybean meal (SBM) with different levels of enzymolysis-fermentation compound protein feed (EFCP) in the diets of growing-finishing pigs, focusing on growth performance, nutrients digestibility, carcass traits, and meat quality. Methods: Sixty DLY (Duroc × Landrace × Yorkshire) pigs with an initial body weight of 42.76 ± 2.05 kg were assigned to 5 dietary treatments in a 2 × 2 + 1 factorial design. These dietary treatments included a corn-soybean meal diet (CON), untreated compound protein feed (UCP) substitution 50% (U50) and 100% SBM (U100) diets, and EFCP substitution 50% (EF50) and 100% SBM (EF100) diets. Each treatment had 6 pens (replicates) with 2 pigs per pen, and the experiment lasted 58 d, divided into phase I (1–28 d) and phase II (29–58 d). Following phase I, only the CON, U50, and EF50 groups were continued for phase II, each with 5 replicate pens. On d 59, a total of 15 pigs (1 pig/pen, 5 pens/treatment) were euthanized. Results: During phase I, the EF50 group had a higher average daily gain (ADG) in pigs (P < 0.05) compared to the CON group, whereas the U50 group did not have a significant difference. As the substitution ratio of UCP and EFCP increased in phase I, there was a noticeable reduction in the final body weight and ADG (P < 0.05), along with an increase in the feed-to-gain ratio (F/G) (P < 0.05). In phase II, there were no significant differences in growth performance among the treatment groups, but EF50 increased the apparent digestibility of several nutrients (including dry matter, crude protein, crude fiber, acid detergent fiber, ash, gross energy) compared to U50. The EF50 group also exhibited significantly higher serum levels of neuropeptide Y and ghrelin compared to the CON and U50 groups (P < 0.05). Moreover, the EF50 group had higher carcass weight and carcass length than those in the CON and U50 groups (P < 0.05), with no significant difference in meat quality. Conclusions: The study findings suggest that replacing 50% SBM with EFCP during the growing-finishing period can improve the growth performance, nutrient digestibility, and carcass traits of pigs without compromising meat quality. This research offers valuable insights into the modification of unconventional plant protein meals and developing alternatives to SBM. [ABSTRACT FROM AUTHOR]

Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho‐deficient (Kl−/−) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl−/− mice. In the salivary glands of embryonic Kl−/− mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO‐1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12‐E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl−/− mice. The ERK inhibitor U0126 specifically inhibited neuronal substance‐induced epithelial bud formation in the embryonic salivary gland. RNA‐seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2‐mediated signaling. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) plays a central role in a variety of emotional and physiological functions in humans, such as forming a part of the body′s response to stress and anxiety. This work compares the impact of MCH and PEG spacer molecules on the performance of a potentiometric NPY sensor. An NPY‐specific DNA aptamer with thiol termination was immobilized onto a gold electrode surface. The performance of the sensor is compared when either an MCH‐ or PEG‐based self‐assembled monolayer is formed following aptamer immobilization. Backfilling the surface with alkanethiol spacer molecules like these is key for proper conformational folding of aptamer‐target binding. Non‐specific adhesion of NPY to the MCH‐based sensor surface was observed via surface plasmon resonance (SPR), and then confirmed via potentiometry. It is then shown that PEG improves the sensor′s sensitivity to NPY compared to the surfaces with an MCH‐based SAM. We achieve the detection of picomolar range NPY levels in buffer with a sensitivity of 36.1 mV/decade for the aptamer and PEG‐based sensor surface, thus demonstrating the promise of potentiometric sensing of NPY for future wearable deployment. The sensor′s selectivity was also studied via exposure to cortisol, a different stress marker, resulting in a 13x smaller differential voltage (aptamer‐specific) response compared to that of NPY. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that has a strong HLA association, where a number of self-epitopes have been implicated in disease pathogenesis. Human pancreatic islet-infiltrating CD4+ T cell clones not only respond to proinsulin C-peptide (PI40-54; GQVELGGGPGAGSLQ) but also cross-react with a hybrid insulin peptide (HIP; PI40-47-IAPP74-80; GQVELGGG-NAVEVLK) presented by HLA-DQ8. How T cell receptors recognize self-peptide and cross-react to HIPs is unclear. We investigated the cross-reactivity of the CD4+ T cell clones reactive to native PI40-54 epitope and multiple HIPs fused at the same N-terminus (PI40-54) to the degradation products of two highly expressed pancreatic islet proteins, neuropeptide Y (NPY68-74) and amyloid polypeptide (IAPP23-29 and IAPP74-80). We observed that five out of the seven selected SKW3 T cell lines expressing TCRs isolated from CD4+ T cells of people with T1D responded to multiple HIPs. Despite shared TRAV26-1-TRBV5-1 gene usage in some T cells, these clones cross-reacted to varying degrees with the PI40-54 and HIP epitopes. Crystal structures of two TRAV26-1+-TRBV5-1+ T cell receptors (TCRs) in complex with PI40-54 and HIPs bound to HLA-DQ8 revealed that the two TCRs had distinct mechanisms responsible for their differential recognition of the PI40-54 and HIP epitopes. Alanine scanning mutagenesis of the PI40-54 and HIPs determined that the P2, P7, and P8 residues in these epitopes were key determinants of TCR specificity. Accordingly, we provide a molecular basis for cross-reactivity towards native insulin and HIP epitopes presented by HLA-DQ8. [ABSTRACT FROM AUTHOR]

Dynamins are large GTPases whose primary function is not only to catalyze membrane scission during endocytosis but also to modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin‐2 mutations, p.A618T, and p.S619L, impair Ca2+‐induced exocytosis of the glucose transporter GLUT4 containing vesicles in immortalized human myoblasts. As exocytosis and endocytosis occur within rapid timescales, here we applied high‐temporal resolution techniques, such as patch‐clamp capacitance measurements and carbon‐fiber amperometry to assess the effects of these mutations on these two cellular processes, using bovine chromaffin cells as a study model. We found that the expression of any of these dynamin‐2 mutants inhibits a dynamin and F‐actin‐dependent form of fast endocytosis triggered by single action potential stimulus, as well as inhibits a slow compensatory endocytosis induced by 500 ms square depolarization. Both dynamin‐2 mutants further reduced the exocytosis induced by 500 ms depolarizations, and the frequency of release events and the recruitment of neuropeptide Y (NPY)‐labeled vesicles to the cell cortex after stimulation of nicotinic acetylcholine receptors with 1,1‐dimethyl‐4‐phenyl piperazine iodide (DMPP). They also provoked a significant decrease in the Ca2+‐induced formation of new actin filaments in permeabilized chromaffin cells. In summary, our results indicate that the centronuclear myopathy (CNM)‐linked p.A618T and p.S619L mutations in dynamin‐2 affect exocytosis and endocytosis, being the disruption of F‐actin dynamics a possible explanation for these results. These impaired cellular processes might underlie the pathogenic mechanisms associated with these mutations. [ABSTRACT FROM AUTHOR]

Objective: To compare the application effects of thoracoscopic assisted anterior mediastinal tumor resection by lateral thoracic approach or subxiphoid approach. Methods: According to the random number table method, 115 patients undergoing thoracoscopic assisted anterior mediastinal tumor resection were divided into group A (n=57, lateral thoracic approach) and group B (n=58, subxiphoid approach). The perioperative related indexes, stress response indexes and inflammatory factors were compared between two groups, and the occurrence of postoperative complications was observed. Results: Compared with group A, group B had longer operation time, less intraoperative blood loss and postoperative drainage volume, shorter postoperative hospital stay and drainage tube indwelling time (P<0.05). 1 day after operation, neuropeptide Y (NPY), 5-hydroxytryptamine (5-HT), substance P (SP) and prostaglandin E2 (PGE2) in two groups increased, but group B were lower than those of group A (P<0.05). 1 day after operation, C-reactive protein (CRP), white blood cell count (WBC) and neutrophils increased in two groups, but group B were lower than those of group A (P<0.05). The total incidence of complications in group A was 12.28%, and that in group B was 6.90%, there was no difference between two groups (P>0.05). Conclusion: During thoracoscopic assisted anterior mediastinal tumor resection, although the subxiphoid approach takes longer than the lateral thoracic approach, which can reduce intraoperative injury, reduce stress response and inflammatory response, and promote postoperative recovery. [ABSTRACT FROM AUTHOR]

Maternal separation can have long-lasting effects on an individual's susceptibility to stress later in life. Maternal separation during the postnatal period is a commonly used paradigm in rodents to investigate the effects of early life stress on neurobehavioural changes and stress responsiveness. However, maternal separation during stress hyporesponsive and responsive periods of postnatal development may differ in its effects on stress resilience. Therefore, we hypothesised that late maternal separation (LMS) from postnatal day 10 to 21 in mice may have different effect on resilience than early maternal separation during the first week of postnatal life. Our results suggested that male LMS mice are more resilient to chronic variable stress (CVS)-induced anxiety and depressive-like behaviour as confirmed by the open field, light-dark field, elevated plus maze, sucrose preference and tail suspension tests. In contrast, female LMS mice were equally resilient as non-LMS female mice. We found increased expression of NPY, NPY1R, NPY2R, NPFFR1, and NPFFR2 in the hypothalamus of male LMS mice whereas the opposite effect was observed in the hippocampus. LMS in male and female mice did not affect circulating corticosterone levels in response to psychological or physiological stressors. Thus, LMS renders male mice resilient to CVS-induced neurobehavioural disorders in adulthood. HIGHLIGHTS: Sexual dimorphism exists in the effects of late maternal separation (LMS) LMS provides resilience to stress-induced anxiety and depression in male mice LMS upregulates NPY and NPVF system in the hypothalamus of male mice No effect of LMS on stress-induced corticosterone levels [ABSTRACT FROM AUTHOR]

Simple Summary: In male rats, the major pelvic ganglion is the principal component of the pelvic plexus and plays a crucial role in regulating various physiological functions such as urination, defecation, erection, ejaculation, and glandular secretion. This ganglion is considered mixed, as it receives both sympathetic and parasympathetic innervation through the hypogastric and pelvic nerves, respectively. Homologous structures with similar functions are present in other species, including cats, dogs, and pigs; however, differences exist in nomenclature, anatomical complexity, and functionality. Although anatomical, histological, and immunohistochemical studies have been conducted on these structures across various species, the major pelvic ganglion of the rat has been the most extensively studied due to its ease of identification and manipulation. This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters, norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species. [ABSTRACT FROM AUTHOR]

Dan Wu,1 Fang Li,2 Feifei Yang,3 Jun Liu4 1Department of Dermatology, Peking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan City, Ningxia Hui Autonomous Region, 750011, People’s Republic of China; 2Department of Pathology, Peking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan City, Ningxia Hui Autonomous Region, 750011, People’s Republic of China; 3Department of Dermatology, Tongzhou Maternal & Child Health Hospital of Beijing, Beijing City, 101101, People’s Republic of China; 4Department of Critical Care Medicine, the First People’s Hospital of Yinchuan, Yinchuan City, Ningxia Hui Autonomous Region, 750001, People’s Republic of ChinaCorrespondence: Jun Liu, Department of Critical Care Medicine, the First People’s Hospital of Yinchuan, No. 2 Liqun West Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, 750001, People’s Republic of China, Email JunLiunnu@outlook.comBackground: Numerous lines of evidence suggest that neuropeptide Y (NPY) is critically involved in the modulation of neuropathic pain. Postherpetic neuralgia (PHN) is characterized by prolonged duration, severe pain, and significant treatment resistance, substantially impairing patients’ quality of life. This study aims to evaluate the potential of plasma NPY levels in patients with PHN as a predictive biomarker for the development of this condition.Methods: Between February 2022 and December 2023, 182 patients with herpes zoster (HZ) were recruited. Thirty-eight volunteers with no history of HZ were also recruited as controls. Clinical factors, NPY, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were assessed within 3 days of healing. Logistic regression analysis was used to predict the development of PHN.Results: NPY levels were lower and BDNF and NGF were higher in HZ patients than those in controls. Only NPY levels were lower in patients with PHN (n = 59) compared with those without PHN (n = 123). Age, acute pain severity, and rash area were independent predictors of PHN, as were NPY levels. The area under the curve (AUC) to predict the development of PHN based on the combination of NPY levels and clinical factors was 0.873 (95% CI: 0.805 to 0.940), and the AUC was 0.804 based on only clinical factors (AUC: 0.804, 95% CI: 0.728 to 0.881).Conclusion: Low plasma NPY levels are a predictor of developing PHN in patients with HZ. Combining clinical predictors with NPY levels may improve predictive accuracy.Keywords: neuropeptide Y, herpes zoster, postherpetic neuralgia, sensory neurons

BACKGROUND: Acupuncture is an effective method for lumbar pain in lumbar disc herniation, but its mechanism has not yet been clarified. Factors related to the JAK2/STAT3 signaling pathway regulate the body’s inflammatory response and are involved in the process of neuropathic pain. OBJECTIVE: To study the mechanism of acupuncture on lumbar disc herniation in a rat model based on the JAK2/STAT3 signaling pathway. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups: sham operation group, model group, acupuncture group, and acupuncture+agonist group, with 10 rats in each group. Animal models of L5 lumbar disc herniation was constructed through autologous disc cell transplantation in the model group, acupuncture group, and acupuncture+agonist group. Rats in the acupuncture group and the acupuncture+agonist group received acupuncture treatment (Yanglingquan, Shenshu, Huantiao, and Dachangshu acupoints) at 3 days after modeling, and acupuncture treatment was given once a day, 20 minutes each, for 15 consecutive days. Rats in the acupuncture+agonist group were injected intrathecally with coumermycin A1, a JAK2 agonist, into the L4/L5 intervertebral space, once a day, 20 minutes each, prior to the acupuncture at 6, 12, and 18 days after modeling. Paw withdrawal mechanical threshold was detected before and 3, 6, 9, 12, 15, and 18 days after modeling. At 18 days after modeling, serum inflammatory factor levels were detected, hematoxylin-eosin staining was performed to observe the morphology of L5-L6 tissues, RT-PCR was performed to detect the expression of JAK2 and STAT3 mRNAs in L5-L6 tissues, and western blot was performed to detect the expression of JAK2, p-JAK2 and p-STAT3 proteins in L5-L6 tissues. RESULTS AND CONCLUSION: The paw withdrawal mechanical thresholds of rats in the model group at different time points after modeling were lower than those in the sham operation group (P < 0.05), the paw withdrawal mechanical thresholds of rats in the acupuncture group were higher than those in the model group at 9, 12, 15, and 18 days after modeling (P < 0.05), and the paw withdrawal mechanical thresholds of rats in the acupuncture+agonist group were lower than those in the acupuncture group at 9, 12, 15, and 18 days after modeling (P < 0.05). The levels of interleukin 6, tumor necrosis factor α, neurotransmitter substance P, and brain neuropeptide Y were elevated in the model group compared with the sham operation group (P < 0.05); the levels of all four inflammatory factors were reduced in the acupuncture group compared with the model group (P < 0.05); and the levels of all four inflammatory factors were elevated in the acupuncture+agonist group compared with the acupuncture group (P < 0.05). Hematoxylin-eosin staining showed that lumbar degeneration was obvious in the model group but reduced in the acupuncture group and the acupuncture+agonist group. Moreover, the reduction was more obvious in the acupuncture group compared with the acupuncture+agonist group. The JAK2 and STAT3 mRNA expression as well as the p-JAK2 and p-STAT3 protein expression were elevated in the model group compared with the sham operation group (P < 0.05), were decreased in the acupuncture group compared with the model group (P < 0.05), and were increased in the acupuncture+agonist group compared with the acupuncture group (P < 0.05). To conclude, acupuncture can alleviate inflammation to exert analgesic effects in the rat model of lumbar disc herniation, and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

The current work attempted to examine the histological and immunohistochemical features of the pancreas in the southern white-breasted hedgehog (Erinaceus concolor). Five adult male individuals were used in this study. Utilizing hematoxylin and eosin as well as Masson's trichrome, staining was performed on paraffin sections of the pancreas. Immunofluorescent staining investigated the expression pattern of glucagon, insulin, somatostatin, neuropeptide Y (NY), and pancreatic polypeptide (PP). The exocrine pancreas comprised pyramidal and oval-shaped acini, exhibiting the clustering of zymogen droplets in the apical cytoplasm of acinar cells. The endocrine pancreas was distinguished as a large α islet of Langerhans and small β islets. Alpha cells were localized on the periphery of islets with an intensity of 20.6% ± 12.56. In comparison, Beta cells with 25.14% ± 5.89 intensity were gathered in the middle of the pancreatic islets. Delta cells exhibited 25.69% ± 5.13 intensity and were distributed through the islets. NY and PP cells were detected with 22.74% ± 3.25 and 16.80% ± 4.77 intensity, respectively. These cells showed prevalent distribution in the islets. In conclusion, it appears that although the pancreas of the southern white-breasted hedgehog is generally like other mammalian species, there are some species-specific features in density and dispersal of endocrine cells which can be attributed to the physiological purpose of the pancreas in this species. Future histophysiological investigations are still needed to explore the exact relationship between the histological organization of the pancreas and its function in that animal. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) and related peptides have been proposed as promising biomarkers for the diagnosis of prostate cancer by previous immunoassays and immunohistochemical studies. In this study, we evaluated the additional value of NPY and related peptides compared with prostate-specific antigen (PSA). We performed a comprehensive analysis of NPY, its precursors, and metabolite concentrations in both plasma and tissue samples from 181 patients using a highly specific liquid chromatography tandem mass spectrometry method. Compared with PSA, NPY and related peptides (NPYs) were less accurate at diagnosing significant prostate cancer. Combinations of NPYs in a stepwise approach did not improve a model that would be beneficial for patients. NPY may be beneficial for patients presenting with a PSA concentration in the gray area between 4 and 9 ng/ml, but the strength of this conclusion is limited. Thus, the use of NPYs as standalone or in combination with other variables, such as PSA, prostate volume, or age, to improve the diagnosis is not supported by our study. Patient summary: This study evaluated neuropeptide Y (NPY) of the family of endogenous peptides as a new biomarker to diagnose prostate cancer. We found that NPY in a patient’s blood was not more helpful at diagnosing prostate cancer than the standard prostate-specific antigen blood test. Further research is needed to explore the potential of NPY and related peptides in specific subgroups of patients.

Abstract Background Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB. Methods In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured. Results In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p

Abstract Background Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small-molecule NPYLR7 agonists that inhibit host-seeking and blood-feeding when fed to mosquitoes at high micromolar doses. Methods Using structure–activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. Results Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified three compounds that reduced blood-feeding from a live host when fed to mosquitoes at a dose of 1 μM—a 100-fold improvement over the original reference compound. Conclusions Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito–human host interactions that lead to pathogen transmission. Graphical Abstract

Abstract Aims Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. Methods and results In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. Conclusions SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines.

Cocaine- and amphetamine- regulated transcript (CART) and Neuropeptide Y (NPY) primarily regulate energy homeostasis. Anurans exhibit diurnal behavioral rhythm, but the response of central neuropeptides to the Day-Night cycle is not elucidated. In this study, we have examined the profile of CART and NPY in the brain of Euphlyctis cyanophlyctis from 6:00 h to 24:00 h. Although expressions of CART and NPY changed with time of the day, circadian oscillation was observed only in expression of CART in anteroventral tegmentum (AV). CART exhibited a single peak in preoptic area (POA), Edinger-Westphal nucleus (EW), nucleus isthmus (NI) and raphe nucleus (Ra); two peaks in ventral hypothamalus (vHy), habenula (Hb) and torus semicircularis (TS). NPY exhibited single peak in TS and suprachiasmatic nucleus (SCN); two peaks in POA, vHy, AV and EW. The daily modulations of these neuropeptides may contribute to their physiological activities and are evolutionarily conserved. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) increases resilience and buffers behavioral stress responses in male rats in part through decreasing the excitability of principal output neurons in the basolateral amygdala (BLA). Intra-BLA administration of NPY acutely increases social interaction (SI) through activation of either Y1 or Y5 receptors, whereas repeated NPY (rpNPY) injections (once daily for 5 d) produce persistent increases in SI through Y5 receptor-mediated neuroplasticity in the BLA. In this series of studies, we characterized the neural circuits from the BLA that underlie these behavioral responses to NPY. Using neuronal tract tracing, NPY Y1 and Y5 receptor immunoreactivity was identified on subpopulations of BLA neurons projecting to the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA). Inhibition of BLA→BNST, but not BLA→CeA, neurons using projection-restricted, cre-driven designer receptors exclusively activated by designer drug-Gi expression increased SI and prevented stress-induced decreases in SI produced by a 30 min restraint stress. This behavioral profile was similar to that seen after both acute and rpNPY injections into the BLA. Intracellular recordings of BLA→BNST neurons demonstrated NPY-mediated inhibition via suppression of H currents, as seen previously. Repeated intra-BLA injections of NPY, which are associated with the induction of BLA neuroplasticity, decreased the activity of BLA→BNST neurons and decreased their dendritic complexity. These results demonstrate that NPY modulates the activity of BNST-projecting BLA neurons, suggesting that this pathway contributes to the stress-buffering actions of NPY and provides a novel substrate for the proresilient effects of NPY. [ABSTRACT FROM AUTHOR]

This experiment was conducted to investigate the effects of coated γ-aminobutyric acid (GABA) on the growth performance, rumen fermentation parameters, and serum hormone levels of lamb. A total of 60 healthy weaned lamb were randomly divided into four groups with three replicates per group and five lambs per replicate. Lambs in each group were fed 0 (control group), 100 (GABA1 group), 150 (GABA2 group) and 200 mg/kg (GABA3 group) coated GABA of diet, respectively. The pre-feeding period was one week and the formal experiment period was four weeks. The results showed that compared with the control group, the final weight and average daily gain of lambs in GABA2 group were significantly increased (P<0.05), and the ratio of feed to gain was significantly decreased (P<0.05). The levels of cholecystokinin in all coated GABA were significantly decreased (P<0.01). The level of neuropeptide Y in GABA2 group and GABA3 group was significantly increased (P<0.05), and the level of norepinephrine was significantly decreased (P<0.05). The level of serotonin in GABA2 group was significantly increased (P<0.05), and the level of dopamine was significantly decreased (P<0.05). The activity of alkaline phosphatase in serum of lambs in GABA2 group was significantly increased (P<0.05), and the activity of glutamic oxalacetic transaminase was significantly decreased (P<0.05). Rumen mycoprotein content in GABA2 group was significantly increased (P<0.05). The study indicates that coated GABA can promote the growth performance of lambs, improve rumen mycoprotein synthesis, improve serum hormone to relieve weaning stress, and the optimal supplemental level is 150 mg/kg. [ABSTRACT FROM AUTHOR]

Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a—known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 μM: 2221 ± 466 μm, control: 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities. [ABSTRACT FROM AUTHOR]

The saccus vasculosus is an organ present in gnathostome fishes, located ventral to the hypothalamus and posterior to the pituitary gland, whose structure is highly variable among species. In some fishes, this organ is well-developed; however, its physiological function is still under debate. Recently, it has been proposed that this organ is a seasonal regulator of reproduction. In the present work, we examined the histology, ultrastructure, and development of the saccus vasculosus in Cichlasoma dimerus. In addition, immunohistochemical studies of proteins related to reproductive function were performed. Finally, the potential response of this organ to different photoperiods was explored. C. dimerus presented a well-developed saccus vasculosus consisting of a highly folded epithelium, composed of coronet and supporting cells, closely associated with blood vessels, and a highly branched lumen connected to the third ventricle. Coronet cells showed all the major characteristics described in other fish species. In addition, some of the vesicles of the globules were positive for thyrotropin beta subunit, while luteinizing hormone beta subunit immunostaining was observed at the edge of the apical processes of some coronet cells. Furthermore, neuropeptide Y and gonadotropin inhibitory hormone innervation in the saccus vasculosus of C. dimerus were shown. Finally, animals exposed to the long photoperiod showed lower levels of thyrotropin beta and common alpha subunits expression in the saccus compared to those of animals exposed to short photoperiod. All these results support the hypothesis that the saccus vasculosus is involved in the regulation of reproductive function in fish. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that neuropeptide signaling shapes auditory computations. We previously showed that neuropeptide Y (NPY) is expressed in the inferior colliculus (IC) by a population of GABAergic stellate neurons and that NPY regulates the strength of local excitatory circuits in the IC. NPY neurons were initially characterized using the NPY-hrGFP mouse, in which humanized renilla green fluorescent protein (hrGFP) expression indicates NPY expression at the time of assay, i.e., an expression-tracking approach. However, studies in other brain regions have shown that NPY expression can vary based on several factors, suggesting that the NPY-hrGFP mouse might miss NPY neurons not expressing NPY on the experiment date. Here, we hypothesized that neurons with the ability to express NPY represent a larger population of IC GABAergic neurons than previously reported. To test this hypothesis, we used a lineage-tracing approach to irreversibly tag neurons that expressed NPY at any point prior to the experiment date. We then compared the physiological and anatomical features of neurons labeled with this lineage-tracing approach to our prior data set, revealing a larger population of NPY neurons than previously found. In addition, we used optogenetics to test the local connectivity of NPY neurons and found that NPY neurons provide inhibitory synaptic input to other neurons in the ipsilateral IC. Together, our data expand the definition of NPY neurons in the IC, suggest that NPY expression might be dynamically regulated in the IC, and provide functional evidence that NPY neurons form local inhibitory circuits in the IC. NEW & NOTEWORTHY: Across brain regions, neuropeptide Y (NPY) expression is dynamic and influenced by extrinsic and intrinsic factors. We previously showed that NPY is expressed by a class of inhibitory neurons in the auditory midbrain. Here, we find that this neuron class also includes neurons that previously expressed NPY, suggesting that NPY expression is dynamically regulated in the auditory midbrain. We also provide functional evidence that NPY neurons contribute to local inhibitory circuits in the auditory midbrain. [ABSTRACT FROM AUTHOR]

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long‐term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long‐term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high‐throughput sequencing and TMT‐tagged LC‐MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long‐term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long‐term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce. [ABSTRACT FROM AUTHOR]

Background: Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB. Methods: In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured. Results: In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, β=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04). Conclusion: This study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major health burden. Preadipocytes proliferate and differentiate in mature adipocytes in the adipogenic process, which could be a potential therapeutic approach for obesity. Deficiency of SIRT6, a stress-responsive protein deacetylase and mono-ADP ribosyltransferase enzyme, blocks adipogenesis. Mutants of SIRT6 (N308K/A313S) were recently linked to the in the long lifespan Ashkenazi Jews. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect adipogenesis at the transcriptional and epigenetic level. Methods: We analyzed the role of SIRT6 wild-type (WT) or SIRT6 centenarian-associated mutant (N308K/A313S) overexpression in adipogenesis, by creating stably transduced preadipocyte cell lines using lentivirus on the 3T3-L1 model. Histone post-translational modifications (PTM: acetylation, methylation) and transcriptomic changes were analyzed by mass spectrometry (LC–MS/MS) and RNA-Seq, respectively, in 3T3-L1 adipocytes. In addition, the adipogenic process and related signaling pathways were investigated by bioinformatics and biochemical approaches. Results: Overexpression of centenarian-associated SIRT6 mutant increased adipogenic differentiation to a similar extent compared to the WT form. However, it triggered distinct histone PTM profiles in mature adipocytes, with significantly higher acetylation levels, and activated divergent transcriptional programs, including those dependent on signaling related to the sympathetic innervation and to PI3K pathway. 3T3-L1 mature adipocytes overexpressing SIRT6 N308K/A313S displayed increased insulin sensitivity in a neuropeptide Y (NPY)-dependent manner. Conclusions: SIRT6 N308K/A313S overexpression in mature adipocytes ameliorated glucose sensitivity and impacted sympathetic innervation signaling. These findings highlight the importance of targeting SIRT6 enzymatic activities to regulate the co-morbidities associated with obesity. [ABSTRACT FROM AUTHOR]

In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection. [ABSTRACT FROM AUTHOR]

The impact of heat stress (HS) on production is intricately linked with feed intake. We investigated the effects of HS on intestines and diencephalic genes in Pekin ducks. One hundred and sixty adult ducks were allocated to two treatment rooms. The control room was maintained at 22°C and the HS room at 35°C for the first 10 h of the day then reduced to 29.5°C. After 3 weeks, 10 hens and 5 drakes were euthanized from each room and jejunum and ileum collected for histology. Brains were collected for gene expression analysis using qRT‐PCR. Intestinal morphology data were analyzed with two‐way ANOVA and diencephalic gene data were analyzed with Kruskal–Wallis test. There was an increase in villi width in the ileum (p = .0136) and jejunum (p = .0019) of HS hens compared to controls. HS drakes showed a higher crypt depth (CD) in the jejunum (p = .0198) compared to controls. There was an increase in crypt goblet cells (GC) count in the ileum (p = .0169) of HS drakes compared to HS hens. There was higher villi GC count (p = .07) in the jejunum of HS drakes compared to controls. There was an increase in the crypt GC density (p = .0054) in the ileum, not jejunum, of HS drakes compared to HS hens. Further, there were no differences in the proopiomelanocortin gene expression in either sex but there was an increase in the expression of neuropeptide Y (NPY) gene in HS hens (p = .031) only and a decrease in the corticotropin releasing hormone gene in the HS drakes (p = .037) compared to controls. These data show that there are sex differences in the effect of HS on gut morphology while the upregulation in NPY gene may suggest a role in mediating response to chronic HS. [ABSTRACT FROM AUTHOR]

During the last few decades, identifying the physiological pathways involved in appetite regulation has become popular among researchers. Although studying feeding regulation in birds, especially in poultry (for breeding purposes) and ornamental birds (for therapeutic purposes), is extremely important, limited experiments have been conducted on these animal models. Until today, more than 50 neurotransmitters affecting birds' appetite have been identified. In the current study, we overviewed the role of one of the most important neural mediators, neuropeptide Y (NPY), in regulating avian appetite. Based on the findings, the presence of this neuropeptide and its receptors in the key areas of food intake regulation, especially the hypothalamus's arcuate nucleus (ARC), has been proven. Numerous studies on birds have repeatedly shown the hyperphagic effects of NPY. Among the different NPY receptors, type 1, 2, and 5 receptors play the most important role in appetite regulation. It has also been observed that the interaction of NPY with neurotransmitters such as glucagon-like peptide-1 (GLP1), vasotocin, bombesin, opioids, alpha-melanocyte-stimulating hormone (α-MSH), cocaine- and amphetamine-regulated transcript (CART) and gamma aminobutyric acid (GABA) is effective in NPY-induced hyperphagia. In addition, the NPY system is also involved in the effects of various mediators such as adiponectin, neuropeptide W (NPW), phoenixin-14, visfatin, adrenomedullin, spexin, kisspeptin, insulin, and somatostatin on appetite regulation. Finally, NPY seems to be one of the most important appetite-stimulating factors in birds and also plays an undeniable role in the effects of other neurotransmitters on appetite regulation. [ABSTRACT FROM AUTHOR]

Introduction: To explore the surgical effect and gastrointestinal functional recovery of laparoscopic-guided total mesorectal excision (LGTME) in patients with rectal cancer. Patients and Methods: A total of 150 rectal cancer patients who underwent surgical treatment in our hospital from July 2022 to July 2023 were selected and randomly divided into two groups using a random number table. There were 75 cases in the control group (CG) who underwent traditional open rectal total mesorectal excision surgery and 75 cases in the experimental group (EG) who underwent LGTME. The surgical effects of the two groups were compared, and the gastrointestinal and anal functional recovery of the two groups were compared before and after treatment. Results: Intraoperative bleeding, incision length, time to initial feeding and time to anal exhaust in the EG were significantly lower than those in the CG (P < 0.05). Before treatment, there was no significant difference in gastrointestinal function and anal function between the two groups(P > 0.05). After treatment, the levels of motilin, gastrin, neuropeptide Y and basic fibroblast growth factor in the EG were significantly higher than those in the CG, with statistical significance (P < 0.05); the maximum anal systolic pressure and resting anal sphincter pressure in the EG were significantly lower than those in the CG (P < 0.05); the rectal sensitivity threshold volume (RSTV) and rectal maximum volume threshold in the EG were significantly higher than those in the CG (P < 0.05). There was no significant difference in most postoperative complications between the two groups (P > 0.05). Conclusion: LGTME improves the surgical effects of rectal cancer patients, promotes the recovery of gastrointestinal function and has a small effect on anal function indicators, thereby reducing hospital stay. [ABSTRACT FROM AUTHOR]

Introduction: While the involvement of neuropeptide Y (NPY) in learning and memory, as well as the role of the Y1 receptor, are well established, the function of the Y2 receptor remains a topic of debate. While the involvement of neuropeptide Y (NPY) in learning and memory, as well as the role of the Y1 receptor, are well established, the function of the Y2 receptor remains a topic of debate. Some studies suggest that NPY may also play a role in autophagy. In our investigation, we aimed to explore whether NPY and its Y2 receptor inhibitor could influence memory modulation or affect Beclin-1 expression in a rat model of Alzheimer’s disease (AD). NPY may also have a role in autophagy, according to some studies. Methods: Intracerebroventricular (i.c.v) injections of amyloid-beta (Aβ1-42, 2µg/µl/ side) were used to establish an animal model of AD. NPY (10 ng/µl, 10 µl, i.c.v) was administered 30 minutes before the retrieval. Y2 antagonist BIIE-0246 was injected 15 minutes before NPY administration in the targeted groups. BIIE-0246 was used at three different concentrations (20 nM, 200 nM, and 2 µM). Passive avoidance memory and novel object recognition were both evaluated. Subsequently, Beclin-1 protein expression in the hippocampus was determined using western blot analysis. Results: It was found that NPY administration improved passive avoidance and cognitive memory in animals treated with Aβ. Injecting BIIE-0246 before NPY did not reverse the improving effect of NPY on passive avoidance and Novel Object Recognition memories. Furthermore, compared to sham-operated animals, Aβ treatment significantly reduced the hippocampal expression of Beclin-1 protein (P≤0.05), and neither NPY nor NPY Y2 receptor inhibitors affected Beclin-1. Conclusion: In Aβ-induced memory impairment, it is thought that NPY can improve both aversive and cognitive memory. Blocking NPY Y2 receptors with BIIE-0246 did not alter NPY’s memory-enhancing effect. [ABSTRACT FROM AUTHOR]

The aim of the article is to briefly describe our work together with Dr. Viktor Mutt. He discovered and purified many new gastrointestinal bioactive neuropeptides that have important applications as therapeutic agents in diabetes, epilepsy, migraine and weight control. Dr. Mutt's strategy was to search for Cterminally amidated peptides. We determined neuropeptide Y equilibrium binding for its receptor. Our work also included the LAla scan of pharmacophores of the neuropeptide galanin (128). Finally, the work led to the establishment of the coexistence of pep tides with small molecule neurotransmitters, such as serotonin, acetylcholine, noradrenaline and dopamine in central and peripheral neurons. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co‐release the agouti‐related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARHAgRP/NPY neurons regulate several hypothalamic–pituitary‐endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARHAgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARHAgRP/NPY neurons on the pattern of GH secretion in fed and food‐deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARHAgRP/NPY neurons (AgRP∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP∆GHR mice. Our findings indicate that short‐term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARHAgRP/NPY neurons. [ABSTRACT FROM AUTHOR]

Our previous research identified interleukin‐4 (IL‐4) as a key regulator of glucose/lipid metabolism, circulatory leptin levels, and insulin action, suggesting its potential as a therapeutic target for obesity and related complications. This study aimed to further elucidate the role of IL‐4 in regulating hypothalamic appetite‐controlling neuropeptides using leptin dysfunctional Leptin145E/145E mice as the experimental model. IL‐4 significantly reduces body weight, food intake, and serum glucose levels. Our data demonstrated that IL‐4 exhibits multiple functions in regulating hypothalamic appetite control, including downregulating orexigenic agouti‐related peptide and neuropeptide Y levels, promoting expression of anorexigenic proopiomelanocortin, alleviating microenvironmental hypothalamic inflammation, enhancing leptin and insulin pathway, and attenuating insulin resistance. Furthermore, IL‐4 promotes uncoupling protein 1 expression of white adipose tissue (WAT), suggesting its role in triggering WAT‐beige switch. In summary, this study uncovers novel function of IL‐4 in mediating food‐intake behaviors and metabolic efficiency by regulating hypothalamic appetite‐control and WAT browning activities. These findings support the therapeutic potential of targeting hypothalamic inflammation and reducing adiposity through IL‐4 intervention for tackling the pandemic increasing prevalence of obesity and associated metabolic disorders. [ABSTRACT FROM AUTHOR]

The neuromodulatory effect of pyroglutamylated RFamide peptide 43 (QRFP43) on the hypothalamic appetite regulation centre in sheep has not yet been investigated. The present work focuses on the role of QRFP43 in modulating mRNA expression of pyroglutamylated RFamide peptide receptor (QRFPR), neuropeptide Y (NPY), agouti related neuropeptide (AGRP), cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT), proopiomelanocortin (POMC), peptidyglycine alpha-amidating monooxygenase (PAM) and NPY protein expression in the hypothalamic arcuate nucleus in sheep. The aim of this study was to investigate whether QRFP43 could affect gene expression of the appetite-regulating centre in the hypothalamus. The experiment was conducted from September to December and included fortyeight female Polish Merino sheep randomly assigned to three groups. The control group received an intracerebrovenctricular infusion of Ringer-Locke solution (480 µl/day), whereas the experimental groups were administered QRFP43 in two doses: 10 or 50 μg/480 μl/day (referred to as the RFa10 and RFa50 groups). Selected brain structures were collected from animals for immunohistochemical and real-time PCR analyses. Central infusions of QRFP43 induced changes in mRNA expression of the NPY, CARTPT, POMC and QRFPR genes. A decrease in NPY and QRFPR mRNA expression, and an increase in CARTPT mRNA expression were detected. Furthermore, infusion of QRFP43 in the RFa50 group resulted in decreased POMC mRNA expression. Our findings suggest that QRFP43 may exert an inhibitory effect on the hypothalamic neuronal network responsible for appetite regulation in sheep. Moreover, it appears that the effect of QRFP43 may vary in different animal species, thus further research is required, especially involving hormonal proteomic analyses. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY), a 36‐amino‐acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]–NPY and [Leu31, Pro34]–NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N‐terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor‐selective drug development. In this study, we report three cryo‐electron microscopy (cryo‐EM) structures of Gi2‐coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]–NPY. Combined with cell‐based assays, our study not only reveals the conserved peptide‐binding mode of NPY receptors but also identifies an additional sub‐pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub‐pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family. [ABSTRACT FROM AUTHOR]

Background: Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small-molecule NPYLR7 agonists that inhibit host-seeking and blood-feeding when fed to mosquitoes at high micromolar doses. Methods: Using structure–activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. Results: Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified three compounds that reduced blood-feeding from a live host when fed to mosquitoes at a dose of 1 μM—a 100-fold improvement over the original reference compound. Conclusions: Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito–human host interactions that lead to pathogen transmission. [ABSTRACT FROM AUTHOR]

Efficient control of feeding behavior requires the coordinated adjustment of complex motivational and affective neurocircuits. Neuropeptides from energy-sensing hypothalamic neurons are potent feeding modulators, but how these endogenous signals shape relevant circuits remains unclear. Here, we examine how the orexigenic neuropeptide Y (NPY) adapts GABAergic inputs to the bed nucleus of the stria terminalis (BNST). We find that fasting increases synaptic connectivity between agouti-related peptide (AgRP)-expressing 'hunger' and BNST neurons, a circuit that promotes feeding. In contrast, GABAergic input from the central amygdala (CeA), an extended amygdala circuit that decreases feeding, is reduced. Activating NPY-expressing AgRP neurons evokes these synaptic adaptations, which are absent in NPY-deficient mice. Moreover, fasting diminishes the ability of CeA projections in the BNST to suppress food intake, and NPY-deficient mice fail to decrease anxiety in order to promote feeding. Thus, AgRP neurons drive input-specific synaptic plasticity, enabling a selective shift in hunger and anxiety signaling during starvation through NPY. Neuropeptides are potent feeding modulators, but how these endogenous signals shape relevant neurocircuits remains unclear. Here, the authors show that hypothalamic neuropeptide Y drives input-specific synaptic plasticity, enabling a selective shift in hunger and anxiety signaling during starvation. [ABSTRACT FROM AUTHOR]

Transition metal sulfides have garnered significant interest in the realm of photoelectrochemical (PEC) sensors due to their remarkable optical and electrical properties. However, their intrinsic UV–vis adsorption and electron‐donor consumption severely hinder their nonirritating and in situ epidermal PEC applications. Herein, a NIR‐808 nm light‐excited heterojunction, phosphomolybdic acid‐encapsulated ytterbium‐doped bismuth sulfide (Yb‐Bi2S3/PMA), is synthesized by hydrothermal method for self‐sufficient electron donor‐based PEC sensing. Further, the Yb‐Bi2S3/PMA heterojunction is decorated on flexible and integrated laser‐induced graphene electrode arrays, providing ultrafast charge carrier transfer capacity and robust mechanical durability (300 bending cycles) for subsequent wearable PEC sensing. As a showcase, the aptamer molecular recognition‐based wearable PEC sensor for sweat trace Neuropeptide Y (NPY, a stress or depression biomarker) presents an ultra‐low detection limit (0.39 fM) and good anti‐interference ability. Moreover, the integration of wearable PEC aptasensor with signal processing and wireless communication facilitates nonirritating and in situ analysis of sweat trace NPY dynamics in various real scenarios (feeding behaviors, physiological stress, and circadian rhythm). More broadly, this research establishes the foundation for NIR‐excitable semiconductors equipped with self‐sufficient electron donor capabilities, unlocking the potential for ultrasensitive wearable PEC sensing applications. [ABSTRACT FROM AUTHOR]

Aquaculturists use polyploid fish to maximize production albeit with some unintended consequences including compromised behaviors and physiological function. Given benefits of probiotic therapies (e.g., improved immune response, growth, and metabolism), we explored probiotic supplementation (mixture of Bifidobacterium, Lactobacillus, and Lactococcus), to overcome drawbacks. We first examined fish gut bacterial community composition using 16S metabarcoding (via principal coordinate analyses and PERMANOVA) and determined probiotics significantly impacted gut bacteria composition (p = 0.001). Secondly, we examined how a genomic disruptor (triploidy) and diet supplements (probiotics) impact gene transcription and behavioral profiles of hatchery‐reared Chinook salmon (Oncorhynchus tshawytscha). Juveniles from four treatment groups (diploid‐regular feed, diploid‐probiotic feed, triploid‐regular feed, and triploid‐probiotic feed; n = 360) underwent behavioral assays to test activity, exploration, neophobia, predator evasion, aggression/sociality, behavioral sensitivity, and flexibility. In these fish, transcriptional profiles for genes associated with neural functions (neurogenesis/synaptic plasticity) and biomarkers for stress response and development (growth/appetite) were (i) examined across treatments and (ii) used to describe behavioral phenotypes via principal component analyses and general linear mixed models. Triploids exhibited a more active behavioral profile (p = 0.002), and those on a regular diet had greater Neuropeptide Y transcription (p = 0.02). A growth gene (early growth response protein 1, p = 0.02) and long‐term neural development genes (neurogenic differentiation factor, p = 0.003 and synaptysomal‐associated protein 25‐a, p = 0.005) impacted activity and reactionary profiles, respectively. Overall, our probiotic treatment did not compensate for triploidy. Our research highlights novel applications of behavioral transcriptomics for identifying candidate genes and dynamic, mechanistic associations with complex behavioral repertoires. [ABSTRACT FROM AUTHOR]