Confined growth of Ultrathin, nanometer-sized FeOOH/CoP heterojunction nanosheet arrays as efficient self-supported electrode for oxygen evolution reaction.

Self-supported electrodes, featuring abundant active species and rapid mass transfer, are promising for practical applications in water electrolysis. However, constructing efficient self-supported electrodes with a strong affinity between the catalytic components and the substrate is of great challenge. In this study, by combining the ideas of in-situ construction and space-confined growth, we designed a novel self-supported FeOOH/cobalt phosphide (CoP) heterojunctions grown on a carefully modified commercial Ni foam (NF) with three-dimensional (3D) hierarchically porous Ni skeleton (FeOOH/CoP/3D NF). The specific porous structure of 3D NF directs the confined growth of FeOOH/CoP catalyst into ultra-thin and small-sized nanosheet arrays with abundant edge active sites. The active FeOOH/CoP component is stably anchored on the rough pore wall of 3D NF support, leading to superior stability and improved conductivity. These structural advantages contributed to a highly facilitated oxygen evolution reaction (OER) activity and enhanced durability of the FeOOH/CoP/3D NF electrode. Herein, the FeOOH/CoP/3D NF electrode afforded a low overpotential of 234 mV at 10 mA cm-2 (41 mV smaller than FeOOH/CoP grown on unmodified Ni foam) and high stability for over 90 h, which is among the top reported OER catalysts. Our study provides an effective idea and technique for the construction of active and robust self-supported electrodes for water electrolysis.

Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Dependence of Interlayer or Sulfur Host on Hollow Framework of Lithium-Sulfur Battery.

Lithium-sulfur batteries are recognized as the next generation of high-specific energy secondary batteries owing to their satisfactory theoretical specific capacity and energy density. However, their commercial application is greatly limited by a series of problems, including disordered migration behavior, sluggish redox kinetics, and the serious shuttle effect of lithium polysulfides. One of the most efficient approaches to physically limit the shuttle effect is the rational design of a hollow framework as sulfur host. However, the influence of the hollow structure on the interlayers has not been clearly reported. In this study, the Mo2 C/C catalysts with hollow(H-Mo2 C/C) and solid(S-Mo2 C/C) frameworks are rationally designed to explore the dependence of the hollow structure on the interlayer or sulfur host. In contrast to the physical limitations of the hollow framework as host, the hollow structure of the interlayer inhibited lithium-ion diffusion, resulting in poor electrochemical properties at high current densities. Based on the superiority of the various frameworks, the H-Mo2 C/C@S | S-Mo2 C/C@PP | Li cells are assembled and displayed excellent electrochemical performance. This work re-examines the design requirements and principles of catalyst frameworks in different battery units.

Blocking cerebral lymphatic system reduces central and peripheral inflammatory response in ischemic stroke.

Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics' role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4+ T lymphocytes, CD8+ T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1ß, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression.

BACKGROUND: Depression is a prevalent psychiatric disorder with high long-term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti-depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about "ATP and depression" especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression. AIM: Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression. CONCLUSION: We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression.

In Vitro Models for Investigating Intestinal Host-Pathogen Interactions.

Infectious diseases are increasingly recognized as a major threat worldwide due to the rise of antimicrobial resistance and the emergence of novel pathogens. In vitro models that can adequately mimic in vivo gastrointestinal physiology are in high demand to elucidate mechanisms behind pathogen infectivity, and to aid the design of effective preventive and therapeutic interventions. There exists a trade-off between simple and high throughput models and those that are more complex and physiologically relevant. The complexity of the model used shall be guided by the biological question to be addressed. This review provides an overview of the structure and function of the intestine and the models that are developed to emulate this. Conventional models are discussed in addition to emerging models which employ engineering principles to equip them with necessary advanced monitoring capabilities for intestinal host-pathogen interrogation. Limitations of current models and future perspectives on the field are presented.

MobileNetV3 network-based diagnosis of caries and periapical periodontitis from periapical films / 口腔疾病防治

Objective@#To research the effectiveness of deep learning techniques in intelligently diagnosing dental caries and periapical periodontitis and to explore the preliminary application value of deep learning in the diagnosis of oral diseases@*Methods@#A dataset containing 2 298 periapical films, including healthy teeth, dental caries, and periapical periodontitis, was used for the study. The dataset was randomly divided into 1 573 training images, 233 validation images, and 492 test images. By comparing various neural network models, the MobileNetV3 network model with better performance was selected for dental disease diagnosis, and the model was optimized by tuning the network hyperparameters. The accuracy, precision, recall, and F1 score were used to evaluate the model's ability to recognize dental caries and periapical periodontitis. Class activation map was used to visualization analyze the performance of the network model@*Results@#The algorithm achieved a relatively ideal intelligent diagnostic effect with precision, recall, and accuracy of 99.42%, 99.73%, and 99.60%, respectively, and the F1 score was 99.57% for classifying healthy teeth, dental caries, and periapical periodontitis. The visualization of the class activation maps also showed that the network model can accurately extract features of dental diseases.@*Conclusion@#The tooth lesion detection algorithm based on the MobileNetV3 network model can eliminate interference from image quality and human factors and has high diagnostic accuracy, which can meet the needs of dental medicine teaching and clinical applications.

Host cellular factors involved in pseudorabies virus attachment and entry: a mini review.

Pseudorabies virus (PRV) belongs to the Alphaherpesvirinae subfamily and serves as an exceptional animal model for investigating the infection mechanism of Herpes simplex virus type 1. Notably, PRV has the capability to infect a wide range of mammals, including humans, highlighting its potential as an overlooked zoonotic pathogen. The attachment and entry steps of PRV into host cells are crucial to accomplish its life cycle, which involve numerous cellular factors. In this mini review, we offer a comprehensive summary of current researches pertaining to the role of cellular factors in PRV attachment and entry stages, with the overarching goal of advancing the development of novel antiviral agents against this pathogen.

Unraveling the Nrf2-ARE Signaling Pathway in the DF-1 Chicken Fibroblast Cell Line: Insights into T-2 Toxin-Induced Oxidative Stress Regulation.

The T-2 toxin (T2) poses a major threat to the health and productivity of animals. The present study aimed to investigate the regulatory mechanism of Nrf2 derived from broilers against T2-induced oxidative damage. DF-1 cells, including those with normal characteristics, as well as those overexpressing or with a knockout of specific components, were exposed to a 24 h treatment of 50 nM T2. The primary objective was to evaluate the indicators associated with oxidative stress and the expression of downstream antioxidant factors regulated by the Nrf2-ARE signaling pathway, at both the mRNA and protein levels. The findings of this study demonstrated a noteworthy relationship between the up-regulation of the Nrf2 protein and a considerable reduction in the oxidative stress levels within DF-1 cells (p < 0.05). Furthermore, this up-regulation was associated with a notable increase in the mRNA and protein levels of antioxidant factors downstream of the Nrf2-ARE signaling pathway (p < 0.05). Conversely, the down-regulation of the Nrf2 protein was linked to a marked elevation in oxidative stress levels in DF-1 cells (p < 0.05). Additionally, this down-regulation resulted in a significant decrease in both the mRNA and protein expression of antioxidant factors (p < 0.05). This experiment lays a theoretical foundation for investigating the detrimental impacts of T2 on broiler chickens. It also establishes a research framework for employing the Nrf2 protein in broiler chicken production and breeding. Moreover, it introduces novel insights for the prospective management of oxidative stress-related ailments in the livestock and poultry industry.

The short- and long-term changes of upper airway and alar in nongrowing patients treated with Mini-Implant Assisted Rapid Palatal Expansion (MARPE): a systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the short- and long-term changes in the upper airway and alar width after mini-implant -assisted rapid palatal expansion (MARPE) in nongrowing patients. METHODS: Five electronic databases (PubMed, Scopus, Embase, Web of Science, and Cochrane Library) were searched up to 2 August, 2023 based on the PICOS principles. The main outcomes were classified into three groups: 1) nasal cavity changes, 2) upper airway changes and 3) alar changes. The mean difference (MD) and 95% confidence intervals (CI) were used to assess these changes. Heterogeneity tests, subgroup analyses, sensitivity analyses, and publication bias were also analyzed. RESULT: Overall, 22 articles were included for data analysis. Nasal cavity width (WMD: 2.05 mm; 95% CI: 1.10, 3.00) and nasal floor width (WMD: 2.13 mm; 95% CI: 1.16, 3.11) increased significantly. While palatopharyngeal volume (WMD: 0.29 cm3, 95% CI: -0.44, 1.01), glossopharyngeal volume (WMD: 0.30 cm3, 95% CI: -0.29, 0.89) and hypopharyngeal volume (WMD: -0.90 cm3; 95% CI: -1.86, 0.06) remained unchanged, nasal cavity volume (WMD: 1.24 cm3, 95% CI: 0.68, 1.81), nasopharyngeal volume (MD: 0.75 cm3, 95% CI: 0.44, 1.06), oropharyngeal volume (WMD: 0.61 cm3, 95% CI: 0.35, 0.87), and total volume of the upper airway (WMD: 1.67 cm3, 95% CI: 0.68, 2.66) increased significantly. Alar width (WMD: 1.47 mm; 95% CI: 0.40, 2.55) and alar base width (WMD: 1.54 mm; 95% CI: 1.21, 1.87) also increased. CONCLUSION: MARPE can increase nasal cavity width, nasal cavity volume, nasopharyngeal volume and oropharyngeal volume for nongrowing patients, but has no significant effect on hypopharyngeal volume. In addition, the alar width also increased. However, the studies included in this meta-analysis were mainly retrospective, nonrandomized and small in number, so the findings should be interpreted with caution and high-quality RCTs need to be studied.

Power amplification for 1.6†µm high-order vortex modes.

1.6 µm high-order vortex modes carrying orbital angular momentums (OAMs) play significant roles in long-range Doppler lidars and other remote sensing. Amplification of 1.6 µm high-order vortex modes is an important way to provide high-power laser sources for such lidars and also enable the weak echo signal to be amplified so that it can be analyzed. In this work, we propose a four-pass Er:YAG vortex master-oscillator-power-amplification (MOPA) system to amplify 1.6 µm high-order vortex modes. In the proof-of-concept experiments, 1.6 µm single OAM mode (l = 3) is amplified successfully and the gain ranging from 1.88 to 2.36 is achieved. Multiplexed OAM mode (l=±3) is also amplified with favorable results. This work addresses the issue as the low gain of Er:YAG vortex MOPA, which provides a feasible path for 1.6 µm high-order vortex modes amplification.

Electrolyte Modulation of Biological Chelation Additives toward a Dendrite-Free Zn Metal Anode.

Aqueous zinc-ion batteries are considered promising energy storage devices due to their superior electrochemical performance. Nevertheless, the uncontrolled dendrites and parasitic side reactions adversely affect the stability and durability of the Zn anode. To cope with these issues, inspired by the chelation behavior between metal ions and amino acids in the biological system, glutamic acid and aspartic acid are selected as electrolyte additives to stabilize the Zn anode. Experimental characterizations in conjunction with theoretical calculation results indicate that these additives can simultaneously modify the solvation structure of hydrated Zn2+ and preferentially adsorb onto the Zn anode, thereby restricting the occurrence of interfacial side reactions and enhancing the performance of the Zn anode. Benefiting from these synergistic effects, the as-assembled Zn-based batteries containing additive electrolytes achieved admirable electrochemical performance. From the viewpoint of electrolyte regulation, this work provides a bright direction toward the development of aqueous batteries.

Chronic unpredictable stress induces depression/anxiety-related behaviors and alterations of hippocampal monoamine receptor mRNA expression in female mice at different ages.

Depression and anxiety are the most common mental health disorders. Though they affect people at any age and occur more often in females, the pathophysiological changes under these conditions are less investigated. In the present study, we examined the effects of age and stress on depression- and anxiety-related behaviors in female mice. Saccharin preference and the open field test were carried out before and after chronic unpredictable stress in 4-, 14- and 25-month-old female mice. After behavioral tests, mRNA levels of monoamine receptors in the hippocampus were measured by real-time RT-PCR. Chronic unpredictable stress decreased saccharin preference in 4-, 14- and 25-month-old mice and the time spent in the center in the open field test in 25-month-old mice. For monoamine receptors, analysis of variance revealed significant effects of age on mRNA levels of Htr1a, Htr2a, Htr6, Adra1a, Adrb2, and Adrb3, significant effects of stress on mRNA levels of Htr4, Adra2c, Adrb1, and Adrb2, and interactions of age × stress on mRNA levels of Htr1a, Htr5b, Adra1d, Adra2a, Adra2c, and Adrb1. Chronic unpredictable stress decreased mRNA levels of Htr4, Htr5b, Adra2c, and Adrb1 in 4-month-old female mice. Correlations were observed between saccharin preference and mRNA levels of Htr4, Htr5b, Htr6, Adra1d, Adra2a, and Adra2c in 4-month-old mice and between the time spent in the center in the open field test and mRNA levels of Htr1b in 4-month-old mice, Htr3a, Htr7, and Adrb2 in 14-month-old mice, and Drd2 in 4- and 14-month-old mice. Our findings support that stress induces depression- and anxiety-related behaviors and the expression of hippocampal monoamine receptors in an age-dependent manner in female mice.

Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats.

Background: Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. Methods: Nitroglycerin (NTG) was used to induce a migraine model in rats, and the model animals were pretreatment with 50 µg/kg and 100 µg/kg perampanel. The expression of pituitary adenylate-cyclase-activating polypeptide (PACAP) was quantified by western blot and quantitative real-time PCR in the trigeminal ganglion, and rat-specific enzyme-linked immunosorbent assay in serum. Western blot was also conducted to explore the effects of perampanel treatment on the phospholipase C (PLC)/protein kinase C (PKC) and protein kinase A (PKA)/cAMP-responsive-element-binding protein (CREB) signaling pathways. Moreover, the cAMP/PKA/CREB-dependent mechanism was evaluated via in vitro stimulation of hippocampal neurons. The cells were treated with perampanel, antagonists and agonists for 24 hours and cell lysates were prepared for western blot analysis. Results: Perampanel treatment notably increased the mechanical withdrawal threshold and decreased head grooming and light-aversive behaviors in NTG-treated rats. It also decreased PACAP expression and affected cAMP/PKA/CREB signaling pathway. However, PLC/PKC signaling pathway may not be involved in this treatment. In in vitro studies, perampanel notably decreased PACAP expression by inhibiting cAMP/PKA/CREB signaling pathway. Conclusions: This study shows that perampanel inhibits the migraine-like pain response and that this beneficial effect might be attributable to regulation of the cAMP/PKA/CREB signaling pathway.

STING-IFN-I pathway relieves incision induced acute postoperative pain via inhibiting the neuroinflammation in dorsal root ganglion of rats.

BACKGROUND: The purpose of this study was to study the effect of STING-IFN-I pathway on incision induced postoperative pain in rats and its possible mechanisms. METHODS: The pain thresholds were evaluated by measuring the mechanical withdrawal threshold and the thermal withdrawal latency. The satellite glial cell and macrophage of DRG were analyzed. The expression of STING, IFN-a, P-P65, iNOS, TNF-α, IL-1ß and IL-6 in DRG was evaluated. RESULTS: The activation of STING-IFN-I pathway can reduce the mechanical hyperalgesia, thermal hyperalgesia, down-regulate the expression of P-P65, iNOS, TNF-α, IL-1ß and IL-6, and inhibit the activation of satellite glial cell and macrophage in DRG. CONCLUSIONS: The activation of STING-IFN-I pathway can alleviate incision induced acute postoperative pain by inhibiting the activation of satellite glial cell and macrophage, which reducing the corresponding neuroinflammation in DRG.

Enhanced lysosomal escape of cell penetrating peptide-functionalized metal-organic frameworks for co-delivery of survivin siRNA and oridonin.

In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named PEG-CPP33@ORI@survivin siRNA@ZIF-90, PEG-CPP33@NPs) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the PEG-CPP33@NPs with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the PEG-CPP33@NPs in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of PEG-CPP33@NPs, demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.

Universal nanosonosensitizer for ROS-mediated reduction of various cancer cells.

Sonodynamic therapy (SDT) has attracted great attention due to its deep tissue penetration, uniform tissue energy distribution, and noninvasiveness features. Additionally, external triggers can precisely focus on the tumor site with good specificity and high controllability. In the past decade, numerous sonosensitizers have been designed and used for SDT. However, the research and development of universal sonosensitizers for many different types of tumors are equally important in clinical treatment. Herein, we synthesized and studied the universality of four MWO4-PEG nanoparticles (NPs). All of the four MWO4-PEG NPs exhibited highly efficient ultrasound (US)-triggered production of 1O2 and ˙OH, enabling effective decreased cell viability, increased cell apoptosis rate, and a destruction of mouse tumors under US stimulation. The US-triggered NPs indicated good sonosensitivity and low toxicity to nine kinds of cancer cells. After accomplishing its therapeutic functions, NiWO4-PEG could be metabolized by the mouse body without any long-term toxicity. The PEGylated MWO4-PEG NPs shown in this study would provide efficient and universal US-triggered cancer therapy with the advantages of a cost-effective, convenient, and noninvasive agent that is promising for noninvasive SDT cancer treatment.

A retrospect and outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.

Studies on the neuroprotective effects of anesthetics were carried out more than half a century ago. Subsequently, many cell and animal experiments attempted to verify the findings. However, in clinical trials, the neuroprotective effects of anesthetics were not observed. These contradictory results suggest a mismatch between basic research and clinical trials. The Stroke Therapy Academic Industry Roundtable X (STAIR) proposed that the emergence of endovascular thrombectomy (EVT) would provide a proper platform to verify the neuroprotective effects of anesthetics because the haemodynamics of patients undergoing EVT is very close to the ischaemia-reperfusion model in basic research. With the widespread use of EVT, it is necessary for us to re-examine the neuroprotective effects of anesthetics to guide the use of anesthetics during EVT because the choice of anesthesia is still based on team experience without definite guidelines. In this paper, we describe the research status of anesthesia in EVT and summarize the neuroprotective mechanisms of some anesthetics. Then, we focus on the contradictory results between clinical trials and basic research and discuss the causes. Finally, we provide an outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.

Fibrinogen-to-albumin ratio percentage: An independent predictor of disease severity and prognosis in anti-N-methyl-D-aspartate receptor encephalitis.

Purpose: This retrospective study aimed to investigate the relationship between fibrinogen-to-albumin ratio percentage (FARP) and disease severity and prognosis in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods: Medical records and clinical characteristics from 181 patients with anti-NMDAR encephalitis were included. The modified Rankin Scale (mRS) was used to analyze disease severity and prognosis at admission and discharge, and correlations between FARP, disease severity, and prognosis were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of FARP in assessing disease severity and prognosis. Results: Compared to the control group, patients with anti-NMDAR encephalitis had higher fibrinogen (Fib) levels (P < 0.001), neutrophil counts (P < 0.001), and FARP levels (P < 0.001) but had lower albumin levels (P = 0.003). The enrolled patients were divided into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge. FARP levels were significantly elevated in the severe group compared to the mild-to-moderate group among patients with anti-NMDAR encephalitis both at admission and discharge (admission 6.0 vs. 7.40, P < 0.001; discharge 6.43 vs. 8.18, P<0.001). Indeed, the mRS scores at admission (56 vs. 26%, P < 0.001) and discharge (26 vs. 11%, P = 0.006) in the high FARP group were significantly higher than those in the low FARP group. Furthermore, FARP was positively correlated with the mRS scores at admission (r = 0.383, P < 0.001) and discharge (r =0.312, P < 0.001). In the multivariate analysis, FARP was significantly associated with disease severity (odds ratio [OR] = 1.416, 95% confidence interval [CI] = 1.117-1.795, P = 0.004) and prognosis (OR = 1.252, 95% CI = 1.010-1.552, P = 0.040). FARP-based ROC curves predicted disease severity, with a sensitivity of 0.756, a specificity of 0.626, and an area under the ROC curve of 0.722 (95% CI = 0.648-0.796, P < 0.001*). The ROC curve predicted the disease prognosis with a sensitivity of 0.703, a specificity of 0.667, and an area under the ROC curve of 0.723 (95% CI = 0.629-0.817, P < 0.001*). Conclusion: Our results indicate that FARP is a novel predictive marker for disease severity and prognosis of anti-NMDAR encephalitis.

Melatonin mediates elevated carbon dioxide-induced photosynthesis and thermotolerance in tomato.

Increasing carbon dioxide (CO2 ) promotes photosynthesis and mitigates heat stress-induced deleterious effects on plants, but the regulatory mechanisms remain largely unknown. Here, we found that tomato (Solanum lycopersicum L.) plants treated with high atmospheric CO2 concentrations (600, 800, and 1000 µmol mol-1 ) accumulated increased levels of melatonin (N-acetyl-5-methoxy tryptamine) in their leaves and this response is conserved across many plant species, including Arabidopsis, rice, wheat, mustard, cucumber, watermelon, melon, and hot pepper. Elevated CO2 (eCO2 ; 800 µmol mol-1 ) caused a 6.8-fold increase in leaf melatonin content, and eCO2 -induced melatonin biosynthesis preferentially occurred through chloroplast biosynthetic pathways in tomato plants. Crucially, manipulation of endogenous melatonin levels by genetic means affected the eCO2 -induced accumulation of sugar and starch in tomato leaves. Furthermore, net photosynthetic rate, maximum photochemical efficiency of photosystem II, and transcript levels of chloroplast- and nuclear-encoded photosynthetic genes, such as rbcL, rbcS, rbcA, psaD, petB, and atpA, significantly increased in COMT1 overexpressing (COMT1-OE) tomato plants, but not in melatonin-deficient comt1 mutants at eCO2 conditions. While eCO2 enhanced plant tolerance to heat stress (42°C) in wild-type and COMT1-OE, melatonin deficiency compromised eCO2 -induced thermotolerance in comt1 plants. The expression of heat shock proteins genes increased in COMT1-OE but not in comt1 plants in response to eCO2 under heat stress. Further analysis revealed that eCO2 -induced thermotolerance was closely linked to the melatonin-dependent regulation of reactive oxygen species, redox homeostasis, cellular protein protection, and phytohormone metabolism. This study unveiled a crucial mechanism of elevated CO2 -induced thermotolerance in which melatonin acts as an essential endogenous signaling molecule in tomato plants.