Collision-free automatic berthing of maritime autonomous surface ships via safety-certified active disturbance rejection control.

This paper addresses the automatic berthing of a maritime autonomous surface ship operating in a confined water environment subject to static obstacles, dynamic obstacles, thruster constraints, and space constraints due to shorelines. A safety-certified active disturbance rejection control (ADRC) method is proposed for achieving the automatic berthing task of an MASS in the presence of model uncertainties and ocean disturbances. An extended state observer (ESO) based on a second-order robust exact differentiator (RED) is employed to estimate an extended state vector consisting of internal model uncertainties and external ocean disturbances. With the aid of the RED-based ESO, a nominal ADRC law is designed to achieve the position and heading stabilization. To avoid collisions with static obstacles, dynamic obstacles, and shorelines, input-to-state safe high-order control barrier functions are used to guarantee safety. Optimized control signals are obtained based on a constrained quadratic programming (QP) problem within safety constraints. In order to translate the control signals into the individual thruster command, a constrained QP problem is further used to search for optimized commands in real time. It is proven that the closed-loop automatic berthing system is input-to-state stable. By using the proposed method, the MASS is able to reach the desired position and heading with collision avoidance. Simulation results verify the effectiveness of the proposed safety-certified ADRC method for automatic berthing.

Healable and conductive sulfur iodide for solid-state Li-S batteries.

Solid-state Li-S batteries (SSLSBs) are made of low-cost and abundant materials free of supply chain concerns. Owing to their high theoretical energy densities, they are highly desirable for electric vehicles1-3. However, the development of SSLSBs has been historically plagued by the insulating nature of sulfur4,5 and the poor interfacial contacts induced by its large volume change during cycling6,7, impeding charge transfer among different solid components. Here we report an S9.3I molecular crystal with I2 inserted in the crystalline sulfur structure, which shows a semiconductor-level electrical conductivity (approximately 5.9 × 10-7 S cm-1) at 25 °C; an 11-order-of-magnitude increase over sulfur itself. Iodine introduces new states into the band gap of sulfur and promotes the formation of reactive polysulfides during electrochemical cycling. Further, the material features a low melting point of around 65 °C, which enables repairing of damaged interfaces due to cycling by periodical remelting of the cathode material. As a result, an Li-S9.3I battery demonstrates 400 stable cycles with a specific capacity retention of 87%. The design of this conductive, low-melting-point sulfur iodide material represents a substantial advancement in the chemistry of sulfur materials, and opens the door to the practical realization of SSLSBs.

Ultrafast universal fabrication of configurable porous silicone-based elastomers by Joule heating chemistry.

Silicone-based elastomers (SEs) have been extensively applied in numerous cutting-edge areas, including flexible electronics, biomedicine, 5G smart devices, mechanics, optics, soft robotics, etc. However, traditional strategies for the synthesis of polymer elastomers, such as bulk polymerization, suspension polymerization, solution polymerization, and emulsion polymerization, are inevitably restricted by long-time usage, organic solvent additives, high energy consumption, and environmental pollution. Here, we propose a Joule heating chemistry method for ultrafast universal fabrication of SEs with configurable porous structures and tunable components (e.g., graphene, Ag, graphene oxide, TiO2, ZnO, Fe3O4, V2O5, MoS2, BN, g-C3N4, BaCO3, CuI, BaTiO3, polyvinylidene fluoride, cellulose, styrene-butadiene rubber, montmorillonite, and EuDySrAlSiOx) within seconds by only employing H2O as the solvent. The intrinsic dynamics of the in situ polymerization and porosity creation of these SEs have been widely investigated. Notably, a flexible capacitive sensor made from as-fabricated silicone-based elastomers exhibits a wide pressure range, fast responses, long-term durability, extreme operating temperatures, and outstanding applicability in various media, and a wireless human-machine interaction system used for rescue activities in extreme conditions is established, which paves the way for more polymer-based material synthesis and wider applications.

Gene inversion led to the emergence of brackish archaeal heterotrophs in the aftermath of the Cryogenian Snowball Earth.

Land-ocean interactions greatly impact the evolution of coastal life on earth. However, the ancient geological forces and genetic mechanisms that shaped evolutionary adaptations and allowed microorganisms to inhabit coastal brackish waters remain largely unexplored. In this study, we infer the evolutionary trajectory of the ubiquitous heterotrophic archaea Poseidoniales (Marine Group II archaea) presently occurring across global aquatic habitats. Our results show that their brackish subgroups had a single origination, dated to over 600 million years ago, through the inversion of the magnesium transport gene corA that conferred osmotic-stress tolerance. The subsequent loss and gain of corA were followed by genome-wide adjustment, characterized by a general two-step mode of selection in microbial speciation. The coastal family of Poseidoniales showed a rapid increase in the evolutionary rate during and in the aftermath of the Cryogenian Snowball Earth (∼700 million years ago), possibly in response to the enhanced phosphorus supply and the rise of algae. Our study highlights the close interplay between genetic changes and ecosystem evolution that boosted microbial diversification in the Neoproterozoic continental margins, where the Cambrian explosion of animals soon followed.

Robust Ionics Reinforced Fiber As Implantable Sensor for Early Operando Monitoring Cell Thermal Safety of Commercial Lithium-Ion Batteries.

Commercial batteries have been largely applied in mobile electronics, electric vehicles, and scalable energy storage systems. However, thermal runaway of batteries still obstructs the reliability of electric equipment. Considering this, building upon recent investigations of energy thermal safety, commercially available organogel fiber-based implantable sensors have been developed through 3D printing technology for first operando implantable monitoring of cell temperature. The printed fibers present excellent reliability and superelasticity because of internal supramolecular cross-linking. High temperature sensitivity (-39.84% °C-1/-1.557% °C-1) within a wide range (-15 to 80 °C) is achieved, and the corresponding mechanism is clarified based on in situ temperature-dependent Raman technology. Furthermore, taking the pouch cell as an example, combined with finite element analysis, the real-time observation system of cell temperature is successfully demonstrated through an implanted sensor with wireless Bluetooth transmission. This enlightening approach paves the way for achieving safety monitoring and smart warnings for various electric equipment.

Self-assembled hydrated copper coordination compounds as ionic conductors for room temperature solid-state batteries.

As the core component of solid-state batteries, neither current inorganic solid-state electrolytes nor solid polymer electrolytes can simultaneously possess satisfactory ionic conductivity, electrode compatibility and processability. By incorporating efficient Li+ diffusion channels found in inorganic solid-state electrolytes and polar functional groups present in solid polymer electrolytes, it is conceivable to design inorganic-organic hybrid solid-state electrolytes to achieve true fusion and synergy in performance. Herein, we demonstrate that traditional metal coordination compounds can serve as exceptional Li+ ion conductors at room temperature through rational structural design. Specifically, we synthesize copper maleate hydrate nanoflakes via bottom-up self-assembly featuring highly-ordered 1D channels that are interconnected by Cu2+/Cu+ nodes and maleic acid ligands, alongside rich COO- groups and structural water within the channels. Benefiting from the combination of ion-hopping and coupling-dissociation mechanisms, Li+ ions can preferably transport through these channels rapidly. Thus, the Li+-implanted copper maleate hydrate solid-state electrolytes shows remarkable ionic conductivity (1.17 × 10-4 S cm-1 at room temperature), high Li+ transference number (0.77), and a 4.7 V-wide operating window. More impressively, Li+-implanted copper maleate hydrate solid-state electrolytes are demonstrated to have exceptional compatibility with both cathode and Li anode, enabling long-term stability of more than 800 cycles. This work brings new insight on exploring superior room-temperature ionic conductors based on metal coordination compounds.

Robust Fiber-Shaped Flexible Temperature Sensors for Safety Monitoring with Ultrahigh Sensitivity.

Flexible temperature sensors capable of detecting and transmitting temperature data from the human body, environment, and electronic devices hold significant potential for applications in electronic skins, human-machine interactions, and disaster prevention systems. Nonetheless, fabricating flexible temperature sensors with exceptional sensing performance remains a formidable task, primarily due to the intricate process of constructing an intrinsically flexible sensing element with high sensitivity. In this study, a facile in situ two-step synthetic method is introduced for fabricating flexible fiber-shaped NiO/carbon nanotube fiber (CNTF) composites. The resulting NiO/CNTF flexible temperature sensors demonstrate outstanding deformability and temperature sensing characteristics, encompassing a broad working range (-15 to 60 °C) and high sensitivity (maximum TCR of -20.2% °C-1 and B value of 3332 K). Importantly, the mechanical and thermal behaviors of the sensor in various application conditions are thoroughly examined using finite element analysis simulations. Moreover, the temperature sensors can effectively capture diverse thermal signals in wearable applications. Notably, a temperature monitoring and warning system is developed to prevent fire accidents resulting from abnormal thermal runaway in electronic devices.

Alternations of antibiotic resistance genes and microbial community dynamics on shared bicycles before and after pandemic lockdown.

The prevalence of shared bicycles has raised concerns over their potential to transmit pathogens and microbes harboring antibiotic resistance genes (ARGs), which pose significant human health risks. This study investigated the impact of anthropogenic activities on the composition of ARGs and microbial communities on shared bicycles during the COVID-19 pandemic and subsequent lockdown when shared bicycle usage was altered. A total of 600 swab samples from shared bicycle surfaces were collected in Shanghai before and during COVID-19 lockdown periods. Even during lockdown, 12 out of 14 initially detected ARG subtypes persisted, indicating their tenacity in the face of reduced anthropogenic activities. These ARGs displayed significantly higher absolute and relative abundance levels before the lockdown. In addition, the percentage of potential pathogens in the total microbial abundance remained at 0.029 % during the lockdown, which was lower than the pre-lockdown percentage of 0.035 % and suggested that these risks persist within shared bicycle systems. Interestingly, although microbial abundance decreased without the consecutive use of shared bicycles during lockdown, the microbial diversity increased under the impact of restricted anthropogenic activities (p < 0.001). This emphasizes the need for continuous monitoring and research to comprehend microbial community behaviors in various environments. This study uncovered the underlying impacts of the COVID-19 lockdown on the microbial and ARG communities of shared bicycles, providing comprehensive insights into the health management of shared transportation. Although lockdown can decrease the abundance of ARGs and potential pathogens, additional interventions are needed to prevent their continued spread.

First-principles prediction of superconducting properties of monolayer 1T'-WS2 under biaxial tensile strain.

High-purity 1T'-WS2 film has been experimentally synthesized [Nature Materials, 20, 1113-1120 (2021)] and theoretically predicted to be a two-dimensional (2D) superconducting material with Dirac cones [arXiv:2301.11425]. In the present work, we further study the superconducting properties of monolayer 1T'-WS2 by applying biaxial tensile strain. It is shown that the superconducting critical temperature Tc firstly increases and then decreases with respect to tensile strains, with the highest superconducting critical temperature Tc of 7.25 K under the biaxial tensile strain of 3%. In particular, we find that Dirac cones also exist in several tensile strained cases. Our studies show that monolayer 1T'-WS2 may provide a good platform for understanding the superconductivity of 2D Dirac materials.

Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemiology, genomic analysis, and instrumental analysis, i.e., to obtain the genomic differential profile of K. pneumoniae strains responsible for two distinct infection outcomes. We found that PLA group had a propensity for specific underlying diseases, especially diabetes and cholelithiasis. The resistance level of VAP was significantly higher than that of PLA (78.57% vs. 36%, P < 0.001), while the virulence results were opposite. There were also some differences in key signaling pathways of biochemical processes between the two groups. The combination of iucA, rmpA, hypermucoviscous phenotype, and ST23 presented in K. pneumoniae infection is more important and highly prudent for timely treatment. The present study may contribute a benchmark for the K. pneumoniae clinical screening, epidemiological surveillance, and effective therapeutic strategies.

Combinational application of the natural products 1-deoxynojirimycin and morin ameliorates insulin resistance and lipid accumulation in prediabetic mice.

BACKGROUND: Prediabetes, a stage characterized by chronic inflammation, obesity and insulin resistance. Morin and 1-deoxynojirimycin (DNJ) are natural flavonoids and alkaloids extracted from Morus nigra L., exhibiting anti-hyperglycemic efficacy. However, the benefits of DNJ are shadowed by the adverse events, and the mechanism of morin in anti-diabetes remains under investigation. PURPOSE: In this study, the combinational efficacy and mechanisms of DNJ and morin in ameliorating insulin resistance and pre-diabetes were investigated. METHODS: The mice model with prediabetes and Alpha mouse liver-12 (AML-12) cell model with insulin resistance were established. The anti-prediabetic efficacy of the drug combination was determined via analyzing the blood glucose, lipid profiles and inflammatory factors. The application of network pharmacology provided guidance for the research mechanism. RESULTS: In our study, the intervention of morin ameliorated the insulin resistance via activating the Peroxisome proliferator-activated receptor γ (PPARγ). However, PPARγ activation leaded to the lipid accumulation in prediabetic mice. The combination of 5 mg/kg dose of DNJ and 25 mg/kg morin effectively hindered the progression of T2DM by 87.56%, which was achieved via inhibition of Suppressors of cytokine signaling 3 (SOCS3) and promotion of PPARγ as well as SOCS2 expression. Furthermore, this treatment exhibited notable capabilities in combating dyslipidemia and adipogenesis, achieved by suppressing the Cluster of differentiation 36/ Sterol-regulatory element binding proteins-1/ Fatty acid synthetase (CD36/Serbp1/Fas) signaling. CONCLUSION: This research confirmed that the drug combination of DNJ and morin in ameliorating insulin resistance and lipid accumulation, and revealed the potential mechanisms. In summary, the combination of DNJ and morin is an underlying alternative pharmaceutical composition in T2DM prevention.

Preoperative Fibrinogen Levels and Function as Predictive Factors for Acute Bleeding in the Hematoma Cavity After Burr Hole Drainage in Patients with CSDH.

OBJECTIVE: Burr hole drainage (BHD) is the primary surgical intervention for managing chronic subdural hematoma (CSDH). However, it can lead to postoperative complications such as acute bleeding within the hematoma cavity and hematoma recurrence. The objective of this study is to identify the risk factors for these complications and develop a predictive model for acute hematoma cavity bleeding after BHD in patients with CSDH. METHODS: This study presents a retrospective cohort investigation conducted at a single center. The clinical dataset of 308 CSDH patients who underwent BHD at a hospital from 2016 to 2022 was analyzed to develop and assess a prognostic model. RESULTS: The nonbleeding group exhibited a significant correlation between fibrinogen (FIB) and thrombin time (TT), whereas no correlation was observed in the bleeding group. Notably, both FIB and TT were identified as risk factors for postoperative acute bleeding within the hematoma cavity. We developed a prognostic model to predict the occurrence of postoperative acute bleeding within the hematoma cavity after BHD in patients with CSDH. The model incorporated FIB, TT, coronary artery disease, and Glasgow Coma Scale scores. The model exhibited good discrimination (area under the curve: 0.725) and calibration (Hosmer-Leeshawn goodness of fit test: P > 0.1). Furthermore, decision curve analysis demonstrated the potential clinical benefit of implementing this prediction model. CONCLUSIONS: The predictive model developed in this study can forecast the risk of postoperative acute bleeding within the hematoma cavity, thus aiding clinicians in selecting the optimal treatment approach for patients with CSDH.

Locally Saturated Ether-Based Electrolytes With Oxidative Stability For Li Metal Batteries Based on Li-Rich Cathodes.

Li metal batteries applying Li-rich, Mn-rich (LMR) layered oxide cathodes present an opportunity to achieve high-energy density at reduced cell cost. However, the intense oxidizing and reducing potentials associated with LMR cathodes and Li anodes present considerable design challenges for prospective electrolytes. Herein, we demonstrate that, somewhat surprisingly, a properly designed localized-high-concentration electrolyte (LHCE) based on ether solvents is capable of providing reversible performance for Li||LMR cells. Specifically, the oxidative stability of the LHCE was found to heavily rely on the ratio between salt and solvating solvent, where local-saturation was necessary to stabilize performance. Through molecular dynamics (MD) simulations, this behavior was found to be a result of aggregated solvation structures of Li+/anion pairs. This LHCE system was found to produce significantly improved LMR cycling (95.8% capacity retention after 100 cycles) relative to a carbonate control as a result of improved cathode-electrolyte interphase (CEI) chemistry from X-ray photoelectron spectroscopy (XPS), and cryogenic transmission electron microscopy (cryo-TEM). Leveraging this stability, 4 mAh cm-2 LMR||2× Li full cells were demonstrated, retaining 87% capacity after 80 cycles in LHCE, whereas the control electrolyte produced rapid failure. This work uncovers the benefits, design requirements, and performance origins of LHCE electrolytes for high-voltage Li||LMR batteries.

A moderately thermophilic origin of a novel family of marine group II euryarchaeota from deep ocean.

Marine group II (MGII) is the most abundant planktonic heterotrophic archaea in the ocean. The evolutionary history of MGII archaea is elusive. In this study, 13 new MGII metagenome-assembled genomes were recovered from surface to the hadal zone in Challenger Deep of the Mariana Trench; four of them from the deep ocean represent a novel group. The optimal growth temperature (OGT) of the common ancestor of MGII has been estimated to be at about 60°C and OGTs of MGIIc, MGIIb, and MGIIa at 47°C-50ºC, 37°C-44ºC, and 30°C-37ºC, respectively, suggesting the adaptation of these species to different temperatures during evolution. The estimated OGT range of MGIIc was supported by experimental measurements of cloned ß-galactosidase that showed optimal enzyme activity around 50°C. These results indicate that MGIIc may have originated from a common ancestor that lived in warm or even hot marine environment, such as hydrothermal vents.

Comparison analysis of safety profiles and identification of risk factors for postoperative adverse reactions: propofol versus sevoflurane in pediatric anesthesia.

OBJECTIVE: To compare the safety profiles between propofol and sevoflurane in pediatric anesthesia and to investigate risk factors for postoperative adverse reactions. METHODS: The data of 194 children who received surgical treatment in Peking Union Medical College Hospital between January 2019 and May 2022 were analyzed retrospectively. According to the different anesthetic drugs the children received, they were divided into a control group (conventional anesthesia with sevoflurane, n=94) and an observation group (anesthesia with both propofol and sevoflurane, n=100). The two groups were compared in terms of anesthetic effect, heart rate, blood oxygen saturation, Ramsay sedation scale (RSS) score during the recovery of anesthesia, and anesthesia safety. Further, the children were grouped based on RSS score to identify the risk factors for agitation during the recovery of anesthesia via logistics regression. RESULTS: The onset time of anesthesia, spontaneous breathing recovery time, extubation time, eye opening time and awake time in the observation group were all significantly shorter than those in the control group (P<0.05). At T1 (during anesthesia induction), T2 (after tracheal intubation) and T3 (after extubation), the observation group showed relatively stable heart rate and blood oxygen saturation than the control group (P<0.05). At the time of awakening, extubation and 30 minutes after extubation, the observation group exhibited significantly lower RSS score than the control group (P<0.05). The observation group also showed a significantly lower incidence of nausea, vomiting and agitation than the control group (P<0.05). Additionally, age ≤6 years old and anesthesia scheme were independent risks for agitation in children during the recovery of anesthesia. The occurrence group had significantly higher risk scores than the non-occurrence group (P<0.05). According to receiver operating characteristic curve-based analysis, the area under the curve of risk score in predicting agitation during the recovery of anesthesia was 0.733. CONCLUSION: Anesthesia with both propofol and sevoflurane is effective in children undergoing surgical treatment, because the combination can substantially reduce the agitation of children during the recovery of anesthesia and has high anesthesia safety. Propofol combined with sevoflurane is a protective factor against agitation in children during the recovery of anesthesia.

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search.

Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra. HypoRiPPAtlas is constructed by mining genomes using seq2ripp, a machine-learning tool for the prediction of ribosomally synthesized and post-translationally modified peptides (RiPPs). In HypoRiPPAtlas, we identify RiPPs in microbes and plants. HypoRiPPAtlas could be extended to other natural product classes in the future by implementing corresponding biosynthetic logic. This study paves the way for large-scale explorations of biosynthetic pathways and chemical structures of microbial and plant RiPP classes.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report.

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

Preparation of Whole-Cut Plant-Based Pork Meat and Its Quality Evaluation with Animal Meat.

Low-moisture (20~40%) and high-moisture (40~80%) textured vegetable proteins (TVPs) can be used as important components of plant-based lean meat, while plant-based fat can be characterized by the formation of gels from polysaccharides, proteins, etc. In this study, three kinds of whole-cut plant-based pork (PBP) were prepared based on the mixed gel system, which were from low-moisture TVP, high-moisture TVP, and their mixtures. The comparisons of these products with commercially available plant-based pork (C-PBP1 and C-PBP2) and animal pork meat (APM) were studied in terms of appearance, taste, and nutritional qualities. Results showed the color changes of PBPs after frying were similar to that of APM. The addition of high-moisture TVP would significantly improve hardness (3751.96~7297.21 g), springiness (0.84~0.89%), and chewiness (3162.44~6466.94 g) while also reducing the viscosity (3.89~10.56 g) of products. It was found that the use of high-moisture TVP led to a significant increase in water-holding capacity (WHC) from 150.25% to 161.01% compared with low-moisture TVP; however, oil-holding capacity (OHC) was reduced from 166.34% to 164.79%. Moreover, essential amino acids (EAAs), the essential amino acids index (EAAI), and biological value (BV) were significantly increased from 272.68 mg/g, 105.52, and 103.32 to 362.65 mg/g, 141.34, and 142.36, respectively, though in vitro protein digestibility (IVPD) reduced from 51.67% to 43.68% due to the high-moisture TVP. Thus, the high-moisture TVP could help to improve the appearance, textural properties, WHC, and nutritional qualities of PBPs compared to animal meat, which was also better than low-moisture TVP. These findings should be useful for the application of TVP and gels in plant-based pork products to improve the taste and nutritional qualities.

Dendrobium officinale Polysaccharide Prevents Diabetes via the Regulation of Gut Microbiota in Prediabetic Mice.

Dendrobium officinale polysaccharide (DOP), which serves as a prebiotic, exhibits a variety of biological activities, including hypoglycemic activities. However, the effects of DOP on diabetes prevention and its hypoglycemic mechanisms are still unclear. In this study, the effects of DOP treatment on the prediabetic mice model were studied and the mechanism was investigated. The results showed that 200 mg/kg/d of DOP reduced the relative risk of type 2 diabetes mellitus (T2DM) from prediabetes by 63.7%. Meanwhile, DOP decreased the level of LPS and inhibited the expression of TLR4 by regulating the composition of the gut microbiota, consequently relieving the inflammation and alleviating insulin resistance. In addition, DOP increased the abundance of SCFA (short chain fatty acid)-producing bacteria in the intestine, increased the levels of intestinal SCFAs, promoted the expression of short-chain fatty acid receptors FFAR2/FFAR3, and increased the secretion of the intestinal hormones GLP-1 and PYY, which helped to repair islet damage, suppress appetite, and improve insulin resistance. Our results suggested that DOP is a promising functional food supplement for the prevention of T2DM.

Glutamatergic melanocortin-4 receptor neurons regulate body weight.

The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVNVGlut2::MC4R and LCVGlut2::MC4R regulation of body weight, and axonal projections of LCVGlut2 neurons remain unclear. Conditional knockout of MC4R in chimeric mice was used to confirm the effects of VGlut2. Interscapular brown adipose tissue was injected with pseudorabies virus to study the central nervous system projections. We mapped the LCVGlut2 circuitry. Based on the Cre-LoxP recombination system, specific knockdown of MC4R in VGlut2 neurons resulted in weight gain in chimeric mice. Adeno-associated virus-mediated knockdown of MC4R expression in the PVN and LC had potential superimposed effects on weight gain, demonstrating the importance of VGlut2 neurons. Unlike these wide-ranging efferent projections, the PVN, hypothalamic arcuate nucleus, supraoptic nucleus of the lateral olfactory tegmental nuclei, and nucleus tractus solitarius send excitatory projections to LCVGlut2 neurons. The PVN → LC glutamatergic MC4R long-term neural circuit positively affected weight management and could help treat obesity.