Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

Design and Optimization of MEMS Resonant Pressure Sensors with Wide Range and High Sensitivity Based on BP and NSGA-II.

With the continuous progress of aerospace, military technology, and marine development, the MEMS resonance pressure sensor puts forward the requirements of not only a wide range but also high sensitivity. However, traditional resonators are hardly compatible with both. In response, we propose a new sensor structure. By arranging the resonant beam and the sensitive diaphragm vertically in space, the new structure improves the rigidity of the diaphragm without changing the thickness of the diaphragm and achieves the purpose of increasing the range without affecting the sensitivity. To find the optimal structural parameters for the sensor sensitivity and range, and to prevent the effects of modal disturbances, we propose a multi-objective optimization design scheme based on the BP and NSGA-II algorithms. The optimization of the structure parameters not only improved the sensitivity but also increased the interference frequency to solve the issue of mode interference. The optimized structure achieves a sensitivity and range of 4.23 Hz/kPa and 1-10 MPa, respectively. Its linear influence factor is 38.07, significantly higher than that of most resonant pressure sensors. The structural and algorithmic optimizations proposed in this paper provide a new method for designing resonant pressure sensors compatible with a wide range and high sensitivity.

Hybrid biomineralized nanovesicles to enhance inflamed lung biodistribution and reduce side effect of glucocorticoid for ARDS therapy.

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs.

In situ neutrophil apoptosis and macrophage efferocytosis mediated by Glycyrrhiza protein nanoparticles for acute inflammation therapy.

In the progression of acute inflammation, the activation and recruitment of macrophages and neutrophils are mutually reinforcing, leading to amplified inflammatory response and severe tissue damage. Therefore, to regulate the axis of neutrophils and macrophages is essential to avoid tissue damage induced from acute inflammatory. Apoptotic neutrophils can regulate the anti-inflammatory activity of macrophages through the efferocytosis. The strategy of in situ targeting and inducing neutrophil apoptosis has the potential to modulate macrophage activity and transfer anti-inflammatory drugs. Herein, a natural glycyrrhiza protein nanoparticle loaded with dexamethasone (Dex@GNPs) was constructed, which could simultaneously regulate neutrophil and macrophage function during acute inflammation treatment by combining in situ neutrophil apoptosis and macrophage efferocytosis. Dex@GNPs can be rapidly and selectively internalized by neutrophils and subsequently induce neutrophils apoptosis through a ROS-dependent mechanism. The efferocytosis of apoptotic neutrophils not only promoted the polarization of macrophages into anti-inflammatory state, but also facilitated the transfer of Dex@GNPs to macrophages. This enabled dexamethasone to further modulate macrophage function. In mouse models of acute respiratory distress syndrome and sepsis, Dex@GNPs significantly ameliorated the disordered immune microenvironment and alleviated tissue injury. This study presents a novel strategy for drug delivery and inflammation regulation to effectively treat acute inflammatory diseases.

A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.

The global threat of multidrug-resistant Gram-negative bacterial pathogens necessitates the development of new and effective antibiotics. FtsZ is an essential and highly conserved cytoskeletal protein that is an appealing antibacterial target for new antimicrobial therapeutics. However, the effectiveness of FtsZ inhibitors against Gram-negative species has been limited due in part to poor intracellular accumulation. To address this limitation, we have designed a FtsZ inhibitor (RUP4) that incorporates a chlorocatechol siderophore functionality that can chelate ferric iron (Fe3+) and utilizes endogenous siderophore uptake pathways to facilitate entry into Gram-negative pathogens. We show that RUP4 is active against both Klebsiella pneumoniae and Acinetobacter baumannii, with this activity being dependent on direct Fe3+ chelation and enhanced under Fe3+-limiting conditions. Genetic deletion studies in K. pneumoniae reveal that RUP4 gains entry through the FepA and CirA outer membrane transporters and the FhuBC inner membrane transporter. We also show that RUP4 exhibits bactericidal synergy against K. pneumoniae when combined with select antibiotics, with the strongest synergy observed with PBP2-targeting ß-lactams or MreB inhibitors. In the aggregate, our studies indicate that incorporation of Fe3+-chelating moieties into FtsZ inhibitors is an appealing design strategy for enhancing activity against Gram-negative pathogens of global clinical significance.

Contrast-enhanced ultrasound evaluation of plaque vulnerability and the relationship between peripheral blood leukocytes.

OBJECTIVE: To evaluate plaque vulnerability by carotid contrast-enhanced ultrasound (CEUS) and to analyze the correlation between plaque vulnerability and peripheral blood leukocyte classification. MATERIALS AND METHODS: 135 patients with carotid plaque were examined by contrast-enhanced ultrasound. Plaque vulnerability was assessed by semiquantitative visual classification. Baseline clinical data and peripheral leukocyte classification were collected. Ordered logistic regression was used to analyze the correlation between plaque neovascularization grade and peripheral leukocyte classification count. RESULTS: There were significant differences in leukocyte, monocyte, neutrophil, mean platelet volume, lymphocyte, and neutrophil counts between different neovascular plaque grades and peripheral blood (P < 0.05). Correlation analysis showed that leukocyte, monocyte, and neutrophil counts were significantly positively correlated. CONCLUSION: The increase in plaque neovascularization is associated with an increase in circulating leukocytes, monocytes, and neutrophils. Therefore, CEUS combined with peripheral blood leukocytes may serve as an early warning of plaque vulnerability and provide a theoretical basis for clinical treatment.

Are electric vehicles really the optimal option for the transportation sector in China to approach pollution reduction and carbon neutrality goals?

Profound worldwide fleet electrification is thought to be the primary route for achieving the target of carbon neutrality. However, when and how electrification can help mitigate environmental impacts and carbon emissions in the transport sector remains unclear. Herein, the overall life-cycle environmental impacts and carbon saving range of two typical A-class vehicles in China, including electric vehicle (EV) and internal combustion engine vehicle (ICEV), were quantified by the life cycle assessment model for endpoint damage with localization parameters. The results showed that the EV outperformed the ICEV for the total environment impact after a travel distance of 39,153 km and for carbon emissions after 32,292 km. The ICEV was more carbon-friendly only when the driving distance was less than 3229 km/a. Considering a full lifespan travel distance of 150,000 km, the whole life-cycle average environmental impacts of EV and ICEV were calculated as 8.6 and 17.5 mPt/km, respectively, but the EV had 2.3 times higher impacts than the ICEV in the production phase. In addition, the EV unit carbon emission was 140 g/km, 46.8% lower than that of the ICEV. Finally, three potential reduction scenarios were considered: cleaner power mix, energy efficiency improvement and composite scenario. These scenarios contributed 19.1%, 13.0% and 32.1% reductions, respectively. However, achieving carbon peak and neutrality goals in China remains a great challenge unless fossil fuels are replaced by renewable energy. The research can provide scientific reference for the method and practice of emission reduction link identification, eco-driving choice and emission reduction path formulation.

Industrial fluoride emissions and their spatial characteristics in the Nansi Lake Basin, Eastern China.

Excessive fluoride emissions threaten ecological stability and human health. Previous studies have noted that industrial sources could be significant. However, quantifying industrial fluoride emissions has not been yet reported. In this study, both bottom-up and top-down approaches were used to estimate the fluoride emissions in the Nansi Lake Basin. Global and local spatial autocorrelation were adopted to reveal the spatial agglomeration effects. The fluoride emissions calculated by the bottom-up approach were larger than those calculated by the top-down method. The highest fluoride input mainly occurred in Zoucheng and Mudan. The highest fluoride emissions mainly occurred in Zoucheng and Rencheng using the bottom-up approach. The highest fluoride emissions mainly occurred in Zoucheng and Yanzhou using the top-down approach. Mining and washing of bituminous coal and anthracite (BAW) was the most significant source of fluoride input and emissions. A significant spatial agglomeration effect of fluoride emissions was found. These findings could provide a method for accurate industrial fluoride emission estimation, complement the critical data on the fluoride emissions of main industrial sectors, and provide a scientific basis for tracing fluoride sources.

Deep-learning architecture for PM2.5 concentration prediction: A review.

Accurately predicting the concentration of fine particulate matter (PM2.5) is crucial for evaluating air pollution levels and public exposure. Recent advancements have seen a significant rise in using deep learning (DL) models for forecasting PM2.5 concentrations. Nonetheless, there is a lack of unified and standardized frameworks for assessing the performance of DL-based PM2.5 prediction models. Here we extensively reviewed those DL-based hybrid models for forecasting PM2.5 levels according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We examined the similarities and differences among various DL models in predicting PM2.5 by comparing their complexity and effectiveness. We categorized PM2.5 DL methodologies into seven types based on performance and application conditions, including four types of DL-based models and three types of hybrid learning models. Our research indicates that established deep learning architectures are commonly used and respected for their efficiency. However, many of these models often fall short in terms of innovation and interpretability. Conversely, models hybrid with traditional approaches, like deterministic and statistical models, exhibit high interpretability but compromise on accuracy and speed. Besides, hybrid DL models, representing the pinnacle of innovation among the studied models, encounter issues with interpretability. We introduce a novel three-dimensional evaluation framework, i.e., Dataset-Method-Experiment Standard (DMES) to unify and standardize the evaluation for PM2.5 predictions using DL models. This review provides a framework for future evaluations of DL-based models, which could inspire researchers to standardize DL model usage in PM2.5 prediction and improve the quality of related studies.

Engineered Biomimetic Nanovesicles Based on Neutrophils for Hierarchical Targeting Therapy of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a clinically severe respiratory disease that causes severe medical and economic burden. To improve therapeutic efficacy, effectively targeting delivery to the inflamed lungs and inflamed cells remains an ongoing challenge. Herein, we designed engineered biomimetic nanovesicles (DHA@ANeu-DDAB) by fusion of lung-targeting functional lipid, neutrophil membrane containing activated ß2 integrins, and the therapeutic lipid, docosahexaenoic acid (DHA). By the advantage of lung targeting lipid and ß2 integrin targeting adhesion, DHA@ANeu-DDAB can first target lung tissue and further target inflammatory vascular endothelial cells, to achieve "tissue first, cell second" hierarchical delivery. In addition, the ß2 integrins in DHA@ANeu-DDAB could bind to the intercellular cell adhesion molecule-1/2 (ICAM-1/2) ligand on the endothelium in the inflamed blood vessels, thus inhibiting neutrophils' infiltration in the blood circulation. DHA administration to inflamed lungs could effectively regulate macrophage phenotype and promote its anti-inflammatory activity via enhanced biosynthesis of specialized pro-resolving mediators. In the lipopolysaccharide-induced ARDS mouse model, DHA@ANeu-DDAB afforded a comprehensive and efficient inhibition of lung inflammation and promoted acute lung damage repair. Through mimicking physiological processes, these engineered biomimetic vesicles as a delivery system possess good potential in targeting therapy for ARDS.

A Ketogenic Diet may Improve Cognitive Function in Rats with Temporal Lobe Epilepsy by Regulating Endoplasmic Reticulum Stress and Synaptic Plasticity.

A ketogenic diet (KD) is often used in the treatment of refractory epilepsy. Many studies have found that it also has a positive impact on cognitive comorbidities, but the specific mechanism remains unclear. In many disease models, endoplasmic reticulum stress (ERS) and synaptic plasticity is considered a new therapeutic target for improving cognitive impairment, and it has become a research focus in recent years. Recently, studies have found that a KD has a certain regulatory effect on both ERS and synaptic plasticity, but this result has not been confirmed in epilepsy. To investigate the effect of a KD on ERS and synaptic plasticity. In this study, a rat model of temporal lobe epilepsy (TLE) induced by lithium chloride-pilocarpine was used. After the model was successfully established, the rats in each group were fed a normal diet or a KD for 28 days, and the effect of a KD on the latency and seizure frequency of spontaneous recurrent seizures (SRSs) was observed via video monitoring. Subsequently, a Morris water maze was used to evaluate the spatial learning and memory abilities of the rats in each group; the ultrastructure of the ER and the synapses of the hippocampus were observed by transmission electron microscopy, and the dendritic spine density of the hippocampus was analysed by Golgi staining. Long-term potentiation (LTP) was used to detect the synaptic plasticity of the rats' hippocampi, and the expression of ERS-related proteins and synapse-related proteins was detected by Western blotting. A KD effectively reduced the frequency of SRSs in rats with TLE and improved their learning and memory impairment. Further investigations found that a KD inhibited the up-regulation of glucose-regulated protein 78, phospho-protein kinase-like ER kinase, phosphorylated α subunit of eukaryotic initiation factor 2, activating transcription factor 4 and C/EBP homologous protein expression in the hippocampi of rats with TLE and protected the ultrastructure of the neuronal ER, suggesting that a KD suppressed excessive ERS induced by epilepsy. Concurrently, we also found that a KD not only improved the synaptic ultrastructure and increased the density of dendritic spines in rats with TLE but also reversed the epilepsy-induced LTP deficit to some extent. More importantly, the expression of postsynaptic density protein 95, synaptotagmin-1 and synaptosomal-associated protein 25 in the hippocampi of rats with epilepsy was significantly increased after KD intervention. The study findings indicate that a KD improves learning and memory impairment in rats with epilepsy, possibly by regulating ERS and synaptic plasticity.

Muti-factor analysis of sport activity level after high tibial osteotomy.

BACKGROUND: Although many studies have shown that high tibial osteotomy is appropriate for active patients, there are limited multifactorial studies on patients' sport activity level after HTO in general population. METHODS: 158 patients who underwent HTO for knee osteoarthritis between January 2016 and December 2019 are included, with a 36-month follow-up. Information was collected from X-rays and questionnaire. The independent variables were age, sex, breadwinner (provide more than 50% income), sport activity level when the knee was pain-free before and after surgery, concomitant meniscal treatment history, Lysholm knee score, desire level for returning to sports. The 158 cases are divided into three groups according to their sports participation before and after operation, Chi-square tests and ANOVA analysis were adopted to identify the effect of these variables on sport activity level after HTO, and factors with statistical differences and clinical relevancies, or provided by previous research were assessed with the ordinal logistic regression analysis. RESULTS: According to sport activity level analysis, 28(17.7%) patients were categorized into the sport level-reduced group, 97(61.4%) patients into the sport level-unchanged group, and 33(20.9%) patients into the sport level-improved group. Upon ordinal logistic regression analysis, postoperative MA%, age, BMI, and preoperative Lysholm knee score were statistically significant. CONCLUSIONS: Higher postoperative MA%, younger age, lower BMI, and lower Lysholm score are associate with improvement on activity level after HTO. This finding provides valuable references in operation option and rehabilitation planning.

Fat body-specific reduction of CTPS alleviates HFD-induced obesity.

Obesity induced by high-fat diet (HFD) is a multi-factorial disease including genetic, physiological, behavioral, and environmental components. Drosophila has emerged as an effective metabolic disease model. Cytidine 5'-triphosphate synthase (CTPS) is an important enzyme for the de novo synthesis of CTP, governing the cellular level of CTP and the rate of phospholipid synthesis. CTPS is known to form filamentous structures called cytoophidia, which are found in bacteria, archaea, and eukaryotes. Our study demonstrates that CTPS is crucial in regulating body weight and starvation resistance in Drosophila by functioning in the fat body. HFD-induced obesity leads to increased transcription of CTPS and elongates cytoophidia in larval adipocytes. Depleting CTPS in the fat body prevented HFD-induced obesity, including body weight gain, adipocyte expansion, and lipid accumulation, by inhibiting the PI3K-Akt-SREBP axis. Furthermore, a dominant-negative form of CTPS also prevented adipocyte expansion and downregulated lipogenic genes. These findings not only establish a functional link between CTPS and lipid homeostasis but also highlight the potential role of CTPS manipulation in the treatment of HFD-induced obesity.

The high rate of obesity has created a global health burden by leading to increased rates of chronic diseases like diabetes and cardiovascular disease. Tackling this issue is complicated as it is influenced by many factors, including genetics, behaviour and environment. To better understand the biochemical changes that underly metabolic issues in a simpler setting, scientists can study fruit flies in the laboratory. These insects share many genes with humans and have similar responses to a high-fat diet. Previous research identified an enzyme, called CTP synthase (CTPS), which is produced in large amounts by the liver and fat tissue in mammals, and the equivalent in fruit flies, known as the fat body. Multiple CTPS molecules can combine to form long strands of protein called cytoophidia, which have been seen in organisms ranging from humans to bacteria. Recent results showed that the fruit fly equivalent of CTPS drives fat cells to stick together, which is necessary to maintain and form fat tissue. However, it is not clear if altering the levels of CTPS can affect the response to a high-fat diet. To address this, Liu, Zhang, Wang et al. studied fruit flies on a high-fat diet, showing that this increased the production of CTPS. When the flies were treated to deplete levels of CTPS in the fat body, they had less body weight gain, smaller fat cells and lower amounts of fats in the body. Genetically modified flies with a version of CTPS that was unable to form cytoophidia also showed fewer signs of obesity, indicating how the enzyme might influence the response to dietary fats. These findings further implicate CTPS in the cause of obesity and help to understand its role. However, it remains to be seen if this also applies to humans. If this is the case, drugs that block the activity of CTPS could help to reduce the impact of a high-fat diet on public health.

Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow.

Chronic heavy alcohol drinking (CHD) rewires monocytes and macrophages toward heightened inflammatory states with compromised antimicrobial defenses that persist after 1-month abstinence. To determine whether these changes are mediated through alterations in the bone marrow niche, we profiled monocytes and hematopoietic stem cell progenitors (HSCPs) from CHD rhesus macaques using a combination of functional assays and single cell genomics. CHD resulted in transcriptional profiles consistent with increased activation and inflammation within bone marrow resident monocytes and macrophages. Furthermore, CHD resulted in transcriptional signatures associated with increased oxidative and cellular stress in HSCP. Differentiation of HSCP in vitro revealed skewing toward monocytes expressing "neutrophil-like" markers with greater inflammatory responses to bacterial agonists. Further analyses of HSCPs showed broad epigenetic changes that were in line with exacerbated inflammatory responses within monocytes and their progenitors. In summary, CHD alters HSCPs in the bone marrow leading to the production of monocytes poised to generate dysregulated hyper-inflammatory responses.

Atorvastatin rescues hyperhomocysteinemia-induced cognitive deficits and neuroinflammatory gene changes.

BACKGROUND: Epidemiological data suggests statins could reduce the risk of dementia, and more specifically, Alzheimer's disease (AD). Pre-clinical data suggests statins reduce the risk of dementia through their pleiotropic effects rather than their cholesterol lowering effects. While AD is a leading cause of dementia, it is frequently found co-morbidly with cerebral small vessel disease and other vascular contributions to cognitive impairment and dementia (VCID), which are another leading cause of dementia. In this study, we determined if atorvastatin ameliorated hyperhomocysteinemia (HHcy)-induced VCID. METHODS: Wild-type (C57Bl6/J) mice were placed on a diet to induce HHcy or a control diet each with or without atorvastatin for 14 weeks. Mice underwent novel object recognition testing before tissue collection. Plasma total cholesterol and total homocysteine as well as related metabolites were measured. Using qPCR and NanoString technology, we profiled glial cell-associated gene expression changes. Finally, microglial morphology, astrocyte end feet, and microhemorrhages were analyzed using histological methods. RESULTS: Atorvastatin treatment of HHcy in mice led to no changes in total cholesterol but decreases in total homocysteine in plasma. While HHcy decreased expression of many glial genes, atorvastatin rescued these gene changes, which mostly occurred in oligodendrocytes and microglia. Microglia in HHcy mice with atorvastatin were trending towards fewer processes compared to control with atorvastatin, but there were no atorvastatin effects on astrocyte end feet. While atorvastatin treatment was trending towards increasing the area of microhemorrhages in HHcy mice in the frontal cortex, it only slightly (non-significantly) reduced the number of microhemorrhages. Finally, atorvastatin treatment in HHcy mice led to improved cognition on the novel object recognition task. CONCLUSIONS: These data suggest that atorvastatin rescued cognitive changes induced by HHcy most likely through lowering plasma total homocysteine and rescuing gene expression changes rather than impacts on vascular integrity or microglial changes.

The neuroprotective effect of Dl-3-n-butylphthalide in epileptic rats via inhibiting endoplasmic reticulum stress.

INTRODUCTION: The purpose of this study is to investigate whether Dl-3-n-Butylphthalide (NBP) has a neuroprotective effect on pilocarpine-induced epileptic (EP) rats through endoplasmic reticulum stress (ERS)-mediated apoptosis. MATERIAL AND METHODS: The Sprague-Dawley rats were divided into four groups: control (CON), EP, EP + NBP 60 (NBP 60 mg/kg) and EP + NBP 120 (NBP 120 mg/kg) groups. After the successful establishment of the temporal lobe EP model using the lithium-pilocarpine, the rats were given NBP for 28 consecutive days in EP + NBP 60 and EP + NBP 120 groups. Then, the spontaneous recurrent seizure (SRS) latency, SRS frequency and seizure duration were observed in each group. In order to observe the abnormal discharge of rats, the intracranial electrodes were implanted to monitor the electroencephalogram. Nissl staining was used to observe the damage to the hippocampal CA1 neurons, TUNEL staining was employed to observe hippocampal neuronal apoptosis. Western blot was used to detect the expression of ERS and ERS-mediated apoptotic proteins. RESULTS: NBP 60 and NBP 120 decreased SRS frequency (all p < 0.05), shortened seizure duration (all p < 0.05), and reduced the abnormal discharge of the brain. Nissl staining and TUNEL staining results show that NBP protected the hippocampal neurons from damage (all p < 0.05) and inhibited hippocampal neuronal apoptosis in EP rats (all p < 0.05). NBP 60 and NBP 120 could reduce ERS and ERS-mediated apoptotic protein expression in EP rats (all p < 0.05). In addition, the therapeutic effect of NBP on epilepsy in rats is dose-dependent. The SRS frequency of the EP + NBP 120 group was lower, and the seizure duration was shorter than in the EP + NBP 60 group (all p < 0.05), and there were more neurons in the EP + NBP 120 group than in the EP + NBP 60 group ( p < 0.05). CONCLUSIONS: NBP had a significant neuroprotective effect in EP rats. Large doses of NBP are more effective than low doses. The mechanism may be associated with the inhibition of ERS and ERS-mediated apoptosis.

Orexin recruits non-selective cationic conductance and endocannabinoid to dynamically modulate firing of caudal pontine reticular nuclear neurones.

The neuropeptide orexin is involved in motor circuit function. However, its modulation on neuronal activities of motor structures, integrating orexin's diverse downstream molecular cascades, remains elusive. By combining whole-cell patch-clamp recordings and neuropharmacological methods, we revealed that both non-selective cationic conductance (NSCC) and endocannabinoids (eCBs) are recruited by orexin signalling on reticulospinal neurones in the caudal pontine reticular nucleus (PnC). The orexin-NSCC cascade provides a depolarizing force that proportionally enhances the firing-responsive gain of these neurones. Meanwhile, the orexin-eCB cascade selectively attenuates excitatory synaptic strength in these neurones by activating presynaptic cannabinoid receptor type 1. This cascade restrains the firing response of the PnC reticulospinal neurones to excitatory inputs. Intriguingly, non-linear or linear interactions between orexin postsynaptic excitation and presynaptic inhibition can influence the firing responses of PnC reticulospinal neurones in different directions. When presynaptic inhibition is in the lead, non-linear interactions can prominently downregulate or even gate the firing response. Conversely, linear interactions occur to promote the firing response, and these linear interactions can be considered a proportional reduction in the contribution of depolarization to firing by presynaptic inhibition. Through the dynamic employment of these interactions, adaptive modulation may be achieved by orexin to restrain or even gate the firing output of the PnC to weak/irrelevant input signals and facilitate those to salient signals. KEY POINTS: This study investigated the effects of orexin on the firing activity of PnC reticulospinal neurones, a key element of central motor control. We found that orexin recruited both the non-selective cationic conductances (NSCCs) and endocannabinoid (eCB)-cannabinoid receptor type 1 (CB1R) system to pontine reticular nucleus (PnC) reticulospinal neurones. The orexin-NSCC cascade exerts a postsynaptic excitation that enhances the firing response, whereas the orexin-eCB-CB1R cascade selectively attenuates excitatory synaptic strength that restrains the firing response. The postsynaptic and presynaptic actions of orexins occur in an overlapping time window and interact to dynamically modulate firings in PnC reticulospinal neurones. Non-linear interactions occur when presynaptic inhibition of orexin is in the lead, and these interactions can prominently downregulate or even gate firing responses in PnC reticulospinal neurones. Linear interactions occur when postsynaptic excitation of orexin is in the lead, and these interactions can promote the firing response. These linear interactions can be considered a proportional reduction of the contribution of depolarization to firing by presynaptic inhibition.

Green solvent mediated extraction of micro- and nano-plastic particles from water.

The production of plastic and the amount of waste plastic that enters the ecosystem increases every year. Synthetic plastics gradually break down into particles on the micro- and nano-scale in the environment. The micro- and nano-plastics pose a significant ecological threat by transporting toxic chemicals and causing inflammation and cellular damage when ingested; however, removal of those particles from water is challenging using conventional separation methods. Deep eutectic solvents (DES), a new class of solvents composed of hydrogen bond donors and acceptors, have been proposed as a cheaper alternative to ionic liquids. Hydrophobic DES derived from natural compounds (NADES) show promise as extractants in liquid-liquid extractions. This study investigated the extraction efficiency of micro- and nano-plastics including polyethylene terephthalate, polystyrene, and a bioplastic polylactic acid from fresh water and saltwater using three hydrophobic NADES. The extraction efficiencies fall in a range of 50-93% (maximum % extraction) while the extraction rates fall between 0.2 and 1.3 h (as indicated by the time to extract half the theoretical maximum). Molecular simulations show a correlation between the extraction efficiency and the association between the plastics and NADES molecules. This study demonstrates the potential of hydrophobic NADES as extractants for removal of different micro- and nano-plastic particles from aqueous solutions.

Genetic mapping and analysis of candidate leaf color genes in common winter wheat (Triticum aestivum L.).

Leaf color-related genes play key roles in chloroplast development and photosynthetic pigment biosynthesis and affect photosynthetic efficiency and grain yield in crops. In this study, a recessive homozygous individual displaying yellow leaf color (yl1) was identified in the progeny population derived from a cross between wheat cultivars Xingmai1 (XM1) and Yunong3114 (YN3114). Phenotypic identification showed that yl1 exhibited the yellow character state over the entire growth period. Compared with XM1, yl1 plants had significantly lower chlorophyll content and net photosynthetic rate, and similar results were found between the green-type lines and yellow-type lines in the BC2F3 XM1 × yl1 population. Gene mapping via the bulked segregant exome capture sequencing (BSE-seq) method showed that the target gene TaYL1 was located within the region of 582,556,971-600,837,326 bp on chromosome 7D. Further analysis by RNA-seq suggested TraesCS7D02G469200 as a candidate gene for yellow leaf color in common wheat, which encodes a protein containing the AP2 domain. Moreover, comparative transcriptome profiling revealed that most differentially expressed genes (DEGs) were enriched in chlorophyll metabolism and photosynthesis pathways. Together, these results indicate that TaYL1 potentially affects chlorophyll synthesis and photosynthesis. This study further elucidates the biological mechanism of chlorophyll synthesis, metabolism, and photosynthesis in wheat and provides a theoretical basis for high photosynthetic efficiency in wheat breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01395-z.

Genomic characterization of two new viruses infecting Ageratum conyzoides in China.

Two new RNA viruses were identified in Ageratum conyzoides in China using high-throughput sequencing, and their genome sequences were determined using PCR and rapid amplification of cDNA ends. The new viruses, which have positive-sense, single-stranded RNA genomes, were provisionally named "ageratum virus 1" (AgV1) and "ageratum virus 2" (AgV2). AgV1 has a genome of 3,526 nucleotides with three open reading frames (ORFs) and shares 49.9% nucleotide sequence identity with the complete genome of Ethiopian tobacco bushy top virus (genus Umbravirus, family Tombusviridae). The genome of AgV2 consists of 5,523 nucleotides and contains five ORFs that are commonly observed in members of the genus Enamovirus of the family Solemoviridae. Proteins encoded by AgV2 exhibited the highest amino acid sequence similarity (31.7-75.0% identity) to the corresponding proteins of pepper enamovirus R1 (an unclassified enamovirus) and citrus vein enation virus (genus Enamovirus). Based on their genome organization, sequence, and phylogenetic relationships, AgV1 is proposed to be a new umbra-like virus of the family Tombusviridae, and AgV2 is proposed to be a new member of the genus Enamovirus of the family Solemoviridae.