Background: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). Methods: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3–6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). Results: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). Conclusions: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge. Full article

Imbibing watermelon seeds in 1 mM sodium tetraborate (Na₂B₄O₇) for 24 h systemically protected plants against foliar infection by Stagonosporopsis cucurbitacearum in detached leaves and under greenhouse conditions. The treatment resulted in both a reduction in the overall percentage of leaf infection as well as in the size of lesions. Studies of the mechanisms by which Na₂B₄O₇ protected watermelon showed that there was no direct effect on the S. cucurbitacearum mycelium growth in vitro. On the other hand, plants raised from seeds primed with Na₂B₄O₇ showed a higher frequency of fluorescent epidermal cells compared to the plants treated with water. This indicates that a higher number of cells expressed the hypersensitive response after Na₂B₄O₇ priming. In addition, there was an increase in peroxidase activity and an enhanced accumulation of a 45 kDa acidic peroxidase isoform during the early stages of infection in plants treated with Na₂B₄O₇ compared to plants treated with water and this was positively correlated to the reduction of leaf infection caused by the pathogen. These results indicate that Na₂B₄O₇ is able to induce systemic resistance in watermelon against S. cucurbitacearum by activating the hypersensitive reaction at penetration sites, increasing peroxidase activity and altering the peroxidase isozyme profile. Although each individual response may only have had a minor effect, their combined effects had a reducing effect on the disease. Full article

Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury. Full article

Antimicrobial stewardship involves a delicate balance between the risk of undertreating individuals and the potential societal burden of overprescribing antimicrobials. This balance is especially crucial in neonatal care. In this observational study, the usefulness of biomarkers of infectious diseases (calprotectin, procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) were evaluated in 141 febrile infants aged 28–90 days presenting to an emergency department. Since our focus was on the usefulness of serum calprotectin, this biomarker was not part of clinical decision-making. A significant difference was observed in the levels of all biomarkers, related to final discharge diagnosis and disposition status. The difference in levels related to antibiotic prescription was significant for all biomarkers but WBCs. The performance of calprotectin in the detection of bacterial infections (AUC (95% CI): 0.804 (0.691, 0.916)) was comparable to the performance of both PCT (0.901 (0.823, 0.980)) and CRP (0.859 (0.764, 0.953)) and superior to the WBC count (0.684 (0.544, 0.823)). Procalcitonin and CRP demonstrated a statistically significantly higher specificity relative to calprotectin. In this cohort, antibiotic use did not always correlate to a definite diagnosis of confirmed bacterial infection. The sample size was limited due to associated challenges with recruiting febrile infants. Hence, there is a need for adequate diagnostic tools to help discriminate between various kinds of infections. This study suggests serum calprotectin, procalcitonin, and CRP may serve as valuable biomarkers to differentiate between types of infection, in addition to clinical input and decision-making. Full article

This article presents a methodology for modeling the impact of both internal and external environmental carbon emission factors on the resulting indicators of an international company. This research uses picture fuzzy rough sets to model the impact of factors on the resulting indicators as a research method. The proposed model is based on a dataset that includes the company’s profit, revenue, valuation, share price, and market share from 2012 through 2022. This empirical period is optimal for such a type of modeling. An approach of picture fuzzy rough sets based on the time series of endogenous and exogenous variables can provide an opportunity to analyze and consider the consequences of feedback changes in the systems of which they are a part. The article proposes a valuable framework for understanding the complex relationship between carbon emissions, economic factors, and the performance of international companies. The researchers of this study recommend a discussion that attempts to gain a deeper understanding of the challenges and opportunities that lie ahead for international companies in the context of climate change and technological innovation. Full article

Recombinant adeno-associated viral (AAV) vectors have emerged as prominent gene delivery vehicles for gene therapy. AAV capsid proteins determine tissue specificity and immunogenicity and play important roles in receptor binding, the escape of the virus from the endosome, and the transport of the viral DNA to the nuclei of target cells. Therefore, the comprehensive characterization of AAV capsid proteins is necessary for a better understanding of the vector assembly, stability, and transduction efficiency of AAV gene therapies. Glycosylation is one of the most common post-translational modifications (PTMs) and may affect the tissue tropism of AAV gene therapy. However, there are few studies on the characterization of the N- and O-glycosylation of AAV capsid proteins. In this study, we identified the N- and O-glycosylation sites and forms of AAV9 capsid proteins generated from HEK293 cells using liquid chromatography–tandem mass spectrometry (LC-MS)-based glycopeptide mapping and identified free N-glycans released from AAV9 capsid proteins by PNGase F using hydrophilic interaction (HILIC) LC-MS and HILIC LC-fluorescence detection (FLD) methods. This study demonstrates that AAV9 capsids are sprinkled with sugars, including N- and O-glycans, albeit at low levels. It may provide valuable information for a better understanding of AAV capsids in supporting AAV-based gene therapy development. Full article

Adequate maternal nutrient intake of vitamin B12 is critical to fetal brain development and subsequent neurodevelopmental outcomes. We conducted a scoping review to map the current state of knowledge from human epidemiological studies on the associations between maternal vitamin B12 during pregnancy and children’s brain, cognitive, language, and motor development to identify gaps in the literature and suggest directions for future research. PubMed and OVID MEDLINE were searched. Search terms were vitamin B12, prenatal or maternal, neurodevelopment or cognitive development or brain. Animal studies were excluded. In total, 148 publications were identified, of which 19 met our inclusion criteria: (1) maternal vitamin B12 assessed via a measure of status, dietary intake, supplementation, or deficiency; and (2) an outcome related to brain development or cognitive, language, or motor development in children less than 18 years of age was assessed. This scoping review suggests that evidence supporting a relationship between maternal vitamin B12 during pregnancy and children’s neurodevelopmental outcomes is inconclusive. Further longitudinal research is needed to clarify the effects of maternal vitamin B12 supplementation, status, and intake on children’s brain development and neurodevelopmental outcomes. Full article

This research investigates the performance of small concrete beams that are reinforced with glass fiber-reinforced polymer (GFRP) bars, basalt fiber-reinforced polymer (BFRP) bars, and traditional steel bars. It addresses the limitations of traditional steel reinforcement, emphasizing the need for alternative strategies. Fiber-reinforced polymer (FRP) materials, including GFRP and BFRP, are examined for their mechanical characteristics compared to steel. The experimental program focuses on ultimate load-bearing capacity, deflection, deformation at different load levels, and failure modes. The concrete specimens, prepared according to Eurocode, consist of six small concrete beams measuring 80 × 120 × 1100 mm with varied reinforcements. The study reveals that GFRP-reinforced beams outperform BFRP and steel reinforcements in ultimate load-bearing capacity, showcasing enhanced structural performance. The GFRP-reinforced beams exhibit capacity and resilience characteristics surpassing those of both BFRP and steel, whereas the deflection observed was higher on both fiber-reinforced beams than on the steel-reinforced beams. The examination of failure modes reveals that the concrete beams that were reinforced with FRP bars showed a bending property before failure, while those reinforced with steel broke easily without bending much. This comprehensive research contributes to advancing our understanding of FRP materials’ application in concrete structures, paving the way for further optimization and overcoming limitations in reinforcement materials. Full article

MEK inhibitors (MEKi) represent innovative and promising treatments for managing manifestations of neurofibromatosis type 1 (NF1). To mitigate potential ophthalmic side effects, such as MEKi-associated retinopathy (MEKAR), patients undergoing MEKi therapy routinely receive ophthalmology evaluations. Our study aims to assess the necessity of this regular screening within a predominantly pediatric NF1 population by examining the occurrence of ocular adverse events (OAE). A retrospective study evaluated 45 NF1 patients receiving MEKi. Inclusion criteria included baseline and follow-up examinations following the initiation of MEKi therapy. At each assessment, a comprehensive eye evaluation was performed, comprising a dilated fundus examination, ocular coherence tomography of the macula and nerve fiber layer, and Humphrey visual field testing. Twenty-six patients, with an average age of 13 years (range 2–23 years) and an average follow-up duration of 413 days were included in the analysis. Three different MEKi were used: selumetinib (77%), trametinib (23%), and mirdametinib (4%). None of the patients experienced retinopathy at any point during the study. Some patients had pre-existing optic neuropathies (27%), but no instances of nerve changes occurred after commencing MEKi therapy. Four patients (15%) exhibited symptoms of dry eye, all of which were effectively managed with topical lubrication. Full article

Three-dimensional (3D) printing of polymer materials encompasses a wide range of applications and innovations. Polymer-based 3D printing, also known as additive manufacturing, has gained significant attention due to its versatility, cost-effectiveness, and potential to revolutionize various industries. The current paper focuses on obtaining a durable low-cost rehabilitation knee orthosis. Researchers propose that the entire structure should be obtained using modern equipment within the additive manufacturing domain—3D printing. The researchers focus on determining, through a 3D analysis of the entire 3D model assembly, which parts present a high degree of stress when a kinematic simulation is developed. The entire 3D model of the orthosis starts based on the result obtained from a 3D scanning of the knee joint of a patient, providing a precise fixation, and allowing for direct personalization. Based on the results and identification of the critical parts, there will be used different materials and a combination of 3D printing strategies to validate the physical model of the entire orthosis. For the manufacturing process, the researchers use two types of low-cost fused filament fabrication (FFF), which are easy to find on the worldwide market. The motivation for manufacturing the entire assembly using 3D printing techniques is the short time in which complex shapes can be obtained, which is relevant for the present study. The main purpose of the present research is to advance orthotic technology by developing an innovative knee brace made of 3D-printed polymers that are designed to be lightweight, easy-to-use, and provide comfort and functionality to patients during the rehabilitation process. Full article

Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little explored. On this basis, as a first approach, in this work, we report that intraperitoneal (i.p.) administration of AMPA or glyphosate (at 10, 56, and 100 mg/kg) decreased, to a similar extent, plasma cholinesterase (ChE) activity in acutely exposed rats. Moreover, we designed an experimental protocol to analyze and compare the effects of AMPA and glyphosate on human plasma ChE activity; this protocol consisted of adding these compounds to human plasma to subsequently test the effects of this plasma on the contraction to acetylcholine (ACh) in the frog rectus abdominis muscle (an indirect estimate of ChE activity). Accordingly, this muscular contraction to ACh was evaluated before and after pre-incubation of ACh with (i) plasma alone, (ii) plasma with AMPA, and (iii) plasma with glyphosate. Our results indicate that AMPA, like glyphosate, decreased ChE activity in the plasma of rats (when given i.p.) and humans (when added in vitro), suggesting that both xenobiotics may exert similar toxicological effects. Full article

As bioindicators, benthic macroinvertebrates are often used to assess stream quality. Based on standard hydrobiological study techniques, the physicochemical and biological health status of the Missolé stream was assessed. Waters of the Missolé stream were found to be slightly acidic (pH: 6.23–6.26) and well-oxygenated (O₂: 69.80–76.80%), with low values of temperature (T°: 23.60–24° C), turbidity (49.40–88.40 FTU) and mineralized ions (NH₄⁺: 0–1.19 mg/L; NO₂^-: 0–1.61 mg/L; NO₃^-: 0.02–6.80 mg/L). Concerning aquatic invertebrate communities, a total of 489 individuals, grouped in two classes, eight orders and 35 families, all belonging to the phylum Arthropoda, were collected and identified. The class of Insecta was the most diversified, with seven orders and 32 families, while that of Crustacea had only one order and three families. Overall, Insecta accounted for 52.35% of the total abundance, and Decapod Crustacea was 47.65%. The three predominant families were Palaemonidae, Dytiscidae and Atyidae. Shannon and Weaver (H’) and Piélou’s evenness (J) indices were high at all stations and showed a slight decrease from upstream to downstream. In the same vein, the Hilsenhoff Biotic Index (HBI) classified the water quality of the Missolé stream as medium. Overall, this suburban aquatic ecosystem offers moderately favorable living conditions for aquatic biota. Full article

While conducting research in a protected ecological reserve within Ecuador’s subtropical rainforest, a 49-year-old biologist, residing in an Andean city, contracted hookworm-related cutaneous larva migrans (Hr-CLM) in the vesiculobullous clinical form. Since there were no domestic dogs or cats in the reserve, it is likely that wild animals carrying Ancylostoma sp. larvae infected the patient. She was effectively treated with two doses of oral ivermectin, administered 31 days after getting the infection. This case was diagnosed in a temperate city; therefore, a comprehensive travel history and clinical assessments are crucial for an accurate diagnosis and timely treatment. Full article

Brazil reported 18,282 suspected congenital Zika syndrome (CZS) cases up to 2018 and accounts for 61.4% of the total reported Zika cases in the Americas in the period. To detect high-risk areas for children with CZS in the city of Rio de Janeiro, we used cluster detection and thematic maps. We analyzed data using a Poisson model in Satscan 10.1.3 software. We also analyzed the records of children with CZS from 2015 to 2016 to describe the clinical and epidemiological maternal and child profile, as well as live births in 2016 and the social development index (SDI) by neighborhood. In 2015 and 2016, the incidence rates of CZS were 8.84 and 46.96 per 100,000 live births in the city, respectively. Severe congenital findings such as microcephaly and brain damage, osteoarticular impairment, ocular abnormalities, and hearing loss were observed in 47 children. The spatial distribution of CZS was concentrated in the north and west zones in heterogeneous neighborhoods. The neighborhoods with the highest occurrence of CZS cases were found to have the worst SDIs. Stascan detected three spatial clusters in the north zone, where the SDI is lower. The clusters presented high relative risks for CZS (7.86, 1.46, and 2.08), although they were not statistically significant. Our findings highlight a higher occurrence of CZS in areas with less favorable socioeconomic conditions. Full article

While digital twins (DTs) have recently gained prominence as a viable option for creating reliable asset representations, many existing frameworks and architectures in the literature involve the integration of different technologies and paradigms, including the Internet of Things (IoTs), data modeling, and machine learning (ML). This complexity requires the orchestration of these different technologies, often resulting in subsystems and composition frameworks that are difficult to seamlessly align. In this paper, we present a scalable compositional framework designed for the development of a DT-based production management system (PMS) with advanced production monitoring capabilities. The conducted approach used to design the compositional framework utilizes the Factory Design and Improvement (FDI) methodology. Furthermore, the validation of our proposed framework is illustrated through a case study conducted in a phosphate screening station within the context of the mining industry. Full article

Background: Additive manufacturing (AM) for patient-specific medical care products offers great opportunities. However, evidence about the supply chain (SC) performance impact based on empirical data is limited. Methods: In this case study, we gathered real-life data about a traditional manufacturing orthopedic shoe SC and developed future scenarios in which AM is introduced at various points and with different degrees of penetration in the SC. Results: Presently, AM can only replace traditional manufacturing of tools and shoe components at a higher total cost. However, with maturing technology, the complete AM production of orthopedic shoes is expected to become feasible. Theoretically, that could disrupt existing SCs, eliminating 70% of the SC steps, improving SC lead time by 90%, and altering SC relations. However, certain thresholds currently prevent disruption. Specifically, the AM of complete orthopedic shoes has to become possible, manufacturing prices have to drop, and traditional craftsmanship has to be integrated into the digital product design. Conclusions: A framework for transition pathways, including directions for future research, is formed. Findings provide valuable insights for scholars and decision makers in the patient-specific products industry, health insurance providers, and healthcare policy makers to be better prepared by adjusting SC designs, relationships, and remuneration programs while AM technology develops towards maturity. Full article

Graphene-based chemical sensors hold promise across diverse applications owing to their exceptional sensitivity and selectivity. However, achieving their long-term durability and reusability while preserving high sensitivity remains a significant challenge, particularly in harsh environments where exposure to strong chemicals is inevitable. This paper presents a novel approach to address this challenge by synergistically integrating liquid-phase exfoliated graphene (LPEG) with polytetrafluoroethylene (PTFE) within a single sensing strip. Through a comprehensive experimental investigation, we demonstrate the fabrication of highly durable and reusable chemical leak detection sensors by combining LPEG and PTFE. Furthermore, we explore the sensing mechanism, highlighting the roles of LPEG and PTFE in enhancing sensitivity and selectivity, along with durability and reusability. Performance evaluation reveals the sensors’ robustness against mechanical and chemical degradation, coupled with excellent recyclability. This innovative approach holds promise for applications in environmental monitoring, industrial safety, and healthcare, thus advancing the field of graphene-based chemical leak detection sensors. Full article

Carbon emissions pose a significant challenge to sustainable development, particularly for China, which is the world’s largest emerging economy and is under pressure to achieve carbon neutrality and reduce emissions amid escalating human activities. The variation in economic development levels and carbon sequestration capacities among its provinces poses a significant hurdle. However, previous research has not adequately examined this dual discrepancy from the perspective of spatial heterogeneity, resulting in a lack of differentiated management of forest carbon sinks across diverse regions. Therefore, to mitigate this discrepancy, this study presents an assessment methodology that analyzes over 100 types of natural and plantation forests using forest age and biomass expansion factors. This study presents a model that can significantly support the efforts of both China and the whole world to achieve carbon neutrality through the improved management of forest carbon sinks. This approach facilitates the assessment of carbon offsets required to meet reduction targets, the development of a provincial framework for carbon intensity and sequestration, and the exploration of their potential for trading markets. Analysis is conducted using MATLAB. Key achievements of this study include the following: (1) The collection of a comprehensive carbon stock dataset for 50 natural and 57 plantation forest types in 31 provinces from 2009 to 2018, highlighting the significant role of new forests in carbon sequestration. (2) The development of a provincial carbon status scoring system that categorizes provinces as carbon-negative, carbon-balancing, or carbon-positive based on local forest sink data and carbon credit demand. (3) The formulation of the carbon intensity–carbon sink assessment (CISA) model, which suggests that provinces with middle- to upper-middle-level economies may have a prolonged need for carbon sink credits during their peak carbon phase. Furthermore, the results show that carbon trading may benefit Guangxi and Yunnan, but may also bring opportunities and risks to Hunan and Hubei. To address regional imbalances, this study advocates tailored policies: carbon-negative and carbon-balancing provinces should enhance carbon sink management, while carbon-positive provinces must focus on energy structure transformation to achieve sustainable development goals. Full article

This study investigates the impact of hospitalist system awareness, motivation, and behavior on value creation within the healthcare context of Taiwan. As population aging and the prevalence of chronic diseases continue to rise, accompanied by increased medical resource consumption, the Taiwan Ministry of Health and Welfare introduced the hospitalist system. Despite its implementation, the number of participating hospitals remains low. Using a questionnaire survey conducted from October 2021 to March 2022, data were collected from medical teams involved in the hospitalist system. A total of 324 valid questionnaires were analyzed. The results reveal that hospitalist awareness positively influences participation motivation (β = 0.846, p < 0.001), which subsequently impacts participation behavior positively (β = 0.888, p < 0.001). Moreover, participation behavior significantly contributes to value creation (β = 0.869, p < 0.001), along with the direct effect of awareness (β = 0.782, p < 0.001) on value creation. In conclusion, the successful promotion and implementation of the hospitalist system rely heavily on the support and active participation of medical staff. Effective interactions and comprehensive information dissemination are essential for maximizing healthcare value creation. Full article

In the study of English denominal adjectives, scholarly attention has predominantly centred on those with Latinate suffixes (e.g., -al, -ary, and -ic/-ical), which are well-known as relational adjectives (RAdjs) and are extensively scrutinised in the existing literature. Conversely, those with English native suffixes (e.g., -en, -ern, -y, and -ed) have not undergone thorough examination to date. In the present study, I delve specifically into denominal adjectives with the suffix -ed (-ed Adjs), such as bearded, long-tailed, and shirt-sleeved. I present a novel basic picture of these adjectives, setting forth the following two central propositions: (i) -ed Adjs are a type of RAdj and (ii) undergo conversion to qualitative adjectives (QAdjs) (e.g., bearded man vs. bearded rock) akin to the better-known Latinate RAdjs (e.g., grammatical error vs. grammatical sentence). The analysis is conducted by examining suffixal etymology (i.e., Latinate or Germanic), suffixal properties (i.e., all-purpose or dedicated), and the driving factor for QAdj-forming conversion (i.e., the modal attribute true). These propositions and analyses collectively enrich our comprehensive understanding of the semantic and morphosyntactic properties of -ed Adjs within the realm of English morphology. Full article

Nitrogen dioxide (NO₂) gas sensors are pivotal in upholding environmental integrity and human health, necessitating heightened sensitivity and exceptional selectivity. Despite the prevalent use of metal oxide semiconductors (MOSs) for NO₂ detection, extant solutions exhibit shortcomings in meeting practical application criteria, specifically in response, selectivity, and operational temperatures. Here, we successfully employed a facile microwave-solvothermal method to synthesize a mesoporous CeO₂/CNCs nanocomposite. This methodology entails the rapid and comprehensive dispersion of CeO₂ nanoparticles onto helical carbon nanocoils (CNCs), resulting in augmented electronic conductivity and an abundance of active sites within the composite. Consequently, the gas-sensing sensitivity of the nanocomposite at room temperature experienced a notable enhancement. Moreover, the presence of cerium oxide and the conversion of Ce³⁺ and Ce⁴⁺ ions facilitated the generation of oxygen vacancies in the composites, thereby further amplifying the sensing performance. Experimental outcomes demonstrate that the nanocomposite exhibited an approximate 9-fold increase in response to 50 ppm NO₂ in comparison to pure CNCs at room temperature. Additionally, the CeO₂/CNCs sensor displayed remarkable selectivity towards NO₂ when exposed to gases such as NH₃, CO, SO₂, CO₂, and C₂H₅OH. This straightforward microwave-solvothermal method presents an appealing strategy for the research and development of intelligent sensors based on CNCs nanomaterials. Full article

Orexin/hypocretin terminals innervate the dorsal raphe nucleus (DRN), which projects to motor control areas important for spontaneous physical activity (SPA) and energy expenditure (EE). Orexin receptors are expressed in the DRN, and obesity-resistant (OR) rats show higher expression of these receptors in the DRN and elevated SPA/EE. We hypothesized that orexin-A in the DRN enhances SPA/EE and that DRN-GABA modulates the effect of orexin-A on SPA/EE. We manipulated orexin tone in the DRN either through direct injection of orexin-A or through the chemogenetic activation of lateral-hypothalamic (LH) orexin neurons. In the orexin neuron activation experiment, fifteen minutes prior to the chemogenetic activation of orexin neurons, the mice received either the GABA-agonist muscimol or antagonist bicuculline injected into the DRN, and SPA/EE was monitored for 24 h. In a separate experiment, orexin-A was injected into the DRN to study the direct effect of DRN orexin on SPA/EE. We found that the activation of orexin neurons elevates SPA/EE, and manipulation of GABA in the DRN does not alter the SPA response to orexin neuron activation. Similarly, intra-DRN orexin-A enhanced SPA and EE in the mice. These results suggest that orexin-A in the DRN facilitates negative energy balance by increasing physical activity-induced EE, and that modulation of DRN orexin-A is a potential strategy to promote SPA and EE. Full article