5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding

Funding Information: The investigators were supported by grants from the NIH (R01DK114279, R01DK109934, and R21NS108091 to QT; R01ES027544 and R01DK111436 to ZS; R00DK107008 to PX; R01DK109194 and R56DK109194 to QW; P01DK113954, R01DK115761, R01DK117281, and R01DK125480 to YX; R01DK120858 to QT and YX; K01DK119471 to CW; and P20GM135002 to YH), USDA/CRIS (51000-064-01 S to YX and QW), American Diabetes Association (1-17-PDF-138 to YH, 7-13-JF-61 to QW, and 1-15-BS-184 to QT), American Heart Association awards (16POST27260254 to CW), the Pew Charitable Trust awards to QW (0026188), Baylor Collaborative Faculty Research Investment Program grants to QW, the Faculty Start-up grants from USDA/ ARS to QW, the Biotechnology and Biological Sciences Research Council (BB/ K001418/1 and BB/NO17838/1 to LKH), and the Medical Research Council (MC/PC/ 15077 to LKH). QW is the Pew Scholar of Biomedical Sciences and the Kavli Scholar. The anxiety tests (e.g., open-field test, light–dark test, and elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. The Ad-iN/ WED virus was kindly provided by Dr. Martin Myers (University of Michigan). The AAV9-CBA-DIO-WGA-zsGreen virus was kindly provided by Dr. Richard Palmiter (University of Washington).Peer reviewedPublisher PD

Analysis of containment pressure control strategy in HPR1000 NPP under severe accidents

Containment is the last barrier of preventing the release of radioactive fission products in a nuclear power plant (NPP). It has the top priority of its strategy in a severe accident (SA) to ensure the integrity of containment. Generally, there are two ways for the containment heat removal. One is to set exchangers or sprays to cool the atmosphere in the containment like CPR1000. The other is to set sprays out of the steel containment to remove heat like AP1000. After Fukushima Daiichi nuclear accident, mitigation strategies after severe accidents are focused and specific systems of dealing with containment failure threat are required to design in new built NPPs. HPR1000 is a generation-Ⅲ PWR in China, which deployed the dedicated severe accident (SA) system of containment spray to address the above conditions. Containment spray in HPR1000 has two identical trains isolated physically, and each train is capable to reduce containment pressure after severe accidents. The containment spray system cannot start automatically, but only be started by operator during severe accidents. According to the lessons from Fukushima accident, it is hard for the operator to make the right choice in such a high-pressure environment during severe accidents, so the proper start-up time is better given in advance as possible. This paper assesses the effectiveness of the containment spray, conducts sensitive calculations of different start-up time, and discuss the negative effects of containment spray. Based on the calculation results, insights of containment spray strategy are gained for HPR1000 NPP and the proper start-up time for the strategy of containment spray in SAMG are put forward

The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration

A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine’s reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect—reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction

Effects of traditional Chinese herbal feed supplement on growth performance, immunity, antioxidant levels, and intestinal health in chickens: a study on Ningdu yellow chickens

ABSTRACT: Traditional Chinese herbs have been widely researched as a green, safe, and effective feed additive for poultry. The purpose of this study was to investigate the effects of traditional Chinese prescription (TCP) based on various herbs in a specific ratio on the growth performance, carcass traits, immunity, antioxidant level, and intestinal health of Ningdu yellow chickens. A total of 420 female Ningdu yellow chickens were randomly divided into 5 groups, with 6 replicates of 14 each. The chickens were fed with a basal diet supplemented with 0 (CON), 0.2, 0.4, 0.6, or 0.8% TCP from d 43 to 105. Body weight, feed intake, and serum biochemical indicators were recorded at d 70 and 105, intestinal morphology and microflora of the carcass were determined at d 105. Compared to the control group, chickens fed with TCP, particularly at the level of 0.6%, showed improved average daily gain and breast muscle percentage, as well as a lower feed-to-gain ratio with statistical significance (P < 0.05). Between 43 and 70 d of age, chickens fed with TCP exhibited higher levels of serum glutathione peroxidase activity, total antioxidant capacity, and superoxide dismutase, particularly in the group fed with the 0.6% level of TCP (P < 0.05). Between 43 and 105 d of age, feeding chickens with 0.4 and 0.6% TCP resulted in a decrease in serum IL-2 concentration, and increase in the IL-4 content (P < 0.05). Chickens fed with 0.4, 0.6, and 0.8% TCP had significantly higher jejunum villous height (P < 0.05), TCP supplementation also led to a marked increase in the relative abundance of Bacteroidota compared to the control group (P < 0.05). Collectively, the study suggests that TCP supplementation can enhance immune and antioxidant functions, improve jejunum morphology, and positively impact cecum microflora in chickens. Based on these results, a level of 0.6% TCP could be considered an optimum level as a feed supplement for Ningdu yellow chickens aged 43 to 105 d

Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions

The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER) stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment

Efficacy of scalp acupuncture combined with conventional therapy in the intervention of post-stroke depression: A systematic review and meta-analysis

Background: Post-stroke depression (PSD) is a common complication following a stroke, significantly impacting patients' quality of life and mental well-being. Currently, two primary approaches are employed to treat PSD: drug therapy and non-drug therapy. Among these, acupuncture, specifically scalp acupuncture (SA), has gained attention due to its cost-effectiveness and broad social benefits. SA is a precise and direct form of acupuncture that has been utilized in the treatment of PSD. Although several randomized controlled trials (RCTs) have demonstrated the efficacy of SA in treating PSD, there is a lack of comprehensive systematic reviews. Given the limitations of existing evidence, we conducted a systematic evaluation to assess the effectiveness of SA in combination with conventional therapy (CT) for intervening in PSD. Methods: We systematically searched five databases for articles published up until May 31, 2023, pertaining to SA treatment of PSD. A team of researchers meticulously screened and assessed these articles to identify the final included studies. After extracting relevant information and outcome indicators from the selected articles, we employed RevMan5.3 software to evaluate their quality and perform statistical analysis. Throughout our research, we strictly adhered to the PRISMA 2020 guidelines. Results: A total of 11 articles were included, and a meta-analysis was conducted to evaluate the effectiveness of SA combined with CT for treating PSD. The results revealed that SA combined with CT can effectively improve the treatment's success rate for PSD and reduce the severity of depressive symptoms measured by the Self-Rating Depression Scale. However, SA combined with CT did not show significant reductions in depressive symptoms assessed by the Hamilton Rating Scale for Depression, which may be related to the inclusion of high heterogeneity articles. Importantly, the combination treatment did not lead to an increase in adverse reactions among PSD patients. Conclusion: While the effectiveness of SA combined with CT in treating PSD still requires further validation through rigorous randomized double-blind trials, this study provides a comprehensive collection of studies that meet the criteria for SA combined with CT in PSD treatment. It objectively and systematically evaluated the impact of SA combined with CT on PSD. Consequently, the findings of this study hold certain clinical significance

Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy

Abstract The CRISPR-Cas9 system offers substantial potential for cancer therapy by enabling precise manipulation of key genes involved in tumorigenesis and immune response. Despite its promise, the system faces critical challenges, including the preservation of cell viability post-editing and ensuring safe in vivo delivery. To address these issues, this study develops an in vivo CRISPR-Cas9 system targeting tumor-associated macrophages (TAMs). We employ bacterial protoplast-derived nanovesicles (NVs) modified with pH-responsive PEG-conjugated phospholipid derivatives and galactosamine-conjugated phospholipid derivatives tailored for TAM targeting. Utilizing plasmid-transformed E. coli protoplasts as production platforms, we successfully load NVs with two key components: a Cas9-sgRNA ribonucleoprotein targeting Pik3cg, a pivotal molecular switch of macrophage polarization, and bacterial CpG-rich DNA fragments, acting as potent TLR9 ligands. This NV-based, self-assembly approach shows promise for scalable clinical production. Our strategy remodels the tumor microenvironment by stabilizing an M1-like phenotype in TAMs, thus inhibiting tumor growth in female mice. This in vivo CRISPR-Cas9 technology opens avenues for cancer immunotherapy, overcoming challenges related to cell viability and safe, precise in vivo delivery

A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism

Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals’ feeding behavior and energy metabolism