Comprehensive metabolic profiling of dioxin-like compounds exposure in laying hens: Implications for toxicity assessment.

The evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress of experimental models based on disease pathogenesis.

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction. To date, no effective treatment exists as the exact causative mechanism remains unknown. Therefore, experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets. Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4, which is highly expressed on the membrane of astrocyte endfeet, most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes. These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders, such as aquaporin-4 loss, astrocytopathy, granulocyte and macrophage infiltration, complement activation, demyelination, and neuronal loss; however, they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders. In this review, we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro, ex vivo, and in vivo for neuromyelitis optica spectrum disorders, suggest potential pathogenic mechanisms for further investigation, and provide guidance on experimental model choices. In addition, this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders, offering further therapeutic targets and a theoretical basis for clinical trials.

Distribution characteristics and sources of ultraviolet absorbents in facility agricultural soils in China.

The environmental contamination of ultraviolet absorbents (UVAs) has attracted global attention for the persistence, bioaccumulation and ecotoxicity. However, little is known about the content and distribution characteristics of UVAs in agricultural soils, especially in facility agricultural soils. In this study, the contents and distribution characteristics of 16 UVAs were surveyed in agricultural facility soils (N = 61) and field soil samples (N = 61) from 27 provinces in China. The total content of 16 UVAs (Σ16UVAs) in facility soils (mean 64.2 ± 55.4 ng/g) was higher than that in field soils (mean 9.66 ± 7.66 ng/g), suggesting that UVAs in facility soils are associated with mulch film. The Σ16UVAs content in the soil mulched with biodegradable (PBAT) film was higher than that in the soil mulched with polyethylene (PE) film, which indicated that the UVA pollution in the soil mulched with biodegradable film was more serious. With the continuous promotion of the use of biodegradable films may pose a threat to soil and ecological health. Therefore, studies on the content and distribution characteristics of UVAs in facility soils are needed to provide scientific basis for the controlling and monitoring of novel pollutants.

A photoelectrochemical aptasensor based on W6+-doped carbon nitride with carbon-rich structure for sensitive detection of diazinon.

A photoelectrochemical (PEC) aptasensor us reported based on W6+-doped carbon nitride with carbon-rich structure (WCCN). WCCN exhibited excellent photoelectric conversion performance owing to the carbon-rich structure and W6+ doping. C atoms can replace the center N/edge N atoms to form a carbon-rich structure, improving the insufficient light absorption of CN in the visible region. Also, W6+ doping forms a directional electron transfer channel, achieving the efficient separation and transport of carriers. W6+ doping and carbon-rich structure can promote the generation, transfer, and separation of photogenerated carriers, further enhancing PEC performance. The fabricated PEC aptasensor based on WCCN demonstrated a wide detection range (3.92 ~ 588 pg L-1), a low detection limit (1.31 pg L-1, S/N = 3), good reproducibility, selectivity, stability, and practical application in actual water samples. This work explores the modification strategy of element doping for carbon nitride with high photoelectric property and offers a cost-effective and simplified method for the detection of pesticide residues.

Manipulation of d-Orbital Electron Configurations in Nonplanar Fe-Based Electrocatalysts for Efficient Oxygen Reduction.

Manipulation of the spin state holds great promise to improve the electrochemical activity of transition metal-based catalysts. However, the underlying relationship between the nonplanar metal coordination environment and spin states remains to be explored. Herein, we report the precise regulation of nonplanar Fe atomic d-orbital energy level into an irregular tetrahedral crystal field configuration by introducing P atoms. With the increase of P coordination number, the spin magnetic moment decreases linearly from 3.8 µB to 0.2 µB, and the high spin content decreases linearly from 31% to 5%. Significantly, a volcanic curve between the spin states of Fe-based catalysts (Fe-NxPy) and oxygen reduction reaction (ORR) activity has been unequivocally established based on the thermodynamic results. Thus, the Fe-N3P1 catalyst with a 19% medium spin state experimentally exhibits the optimal reaction activity with a high half-wave potential of 0.92 V. These findings indicate that regulating electron spin moments through coordination engineering is a promising catalyst design strategy, providing important insights into spin catalysis.

Application and Research Progress of Laser-Induced Breakdown Spectroscopy in Agricultural Product Inspection.

The quality and safety of agricultural products are of paramount importance in ensuring the health of the food supply chain. Additionally, the composition and trace elements in agricultural products significantly influence their quality and nutritional value. Therefore, the need for rapid and accurate analysis techniques for agricultural product composition is particularly crucial. In the current landscape of evolving compositional analysis technologies, Laser-Induced Breakdown Spectroscopy (LIBS) technology is emerging as a promising analytical tool with broad applications in agricultural product testing. Its characteristics of being rapid, real-time, and capable of simultaneous detection of multiple elements provide an efficient and reliable means for assessing the quality, monitoring safety, and tracing the origin of agricultural products. This technology is expected to play a significant role in controlling and managing the agricultural industry chain and can offer consumers safer and healthier agricultural products. This paper provides an overview of the research status and recent developments of LIBS technology in agricultural product testing applications in recent years. Based on the current research landscape, challenges and opportunities of applying LIBS technology in fields such as agricultural product quality and safety assessment, soil analysis, assessment of crop nutrition, detection of plant diseases, and identification of agricultural product varieties have been evaluated. Moreover, recommendations for further expanding the application of LIBS technology in the agricultural sector are proposed.

A fine-grained image classification algorithm based on self-supervised learning and multi-feature fusion of blood cells.

Leukemia is a prevalent and widespread blood disease, and its early diagnosis is crucial for effective patient treatment. Diagnosing leukemia types heavily relies on pathologists' morphological examination of blood cell images. However, this process is tedious and time-consuming, and the diagnostic results are subjective, leading to potential misdiagnosis and underdiagnosis. This paper proposes a blood cell image classification method that combines MAE with an enhanced Vision Transformer to tackle these challenges. Initially, pre-training occurs on two datasets, TMAMD and Red4, using the MAE self-supervised learning algorithm. Subsequently, the pre-training weights are transferred to our improved model.This paper introduces feature fusion of the outputs from each layer of the Transformer encoder to maximize the utilization of features extracted from lower layers, such as color, contour, and texture of blood cells, along with deeper semantic features. Furthermore, the dynamic margins for the subcenter Arcface Loss function are employed to enhance the model's fine-grained feature representation by achieving inter-class dispersion and intra-class aggregation. Models trained using our method achieved state-of-the-art results on both the TMAMD dataset and Red4 dataset, with classification accuracies of 93.51% and 81.41%, respectively. This achievement is expected to be a valuable reference for physicians in their clinical diagnoses.

Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone.

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Colchicine prevents perioperative myocardial injury in cardiac surgery by inhibiting the formation of neutrophil extracellular traps: evidence from rat models.

OBJECTIVES: Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps release. However, its role in cardiac surgery and the mechanisms behind neutrophil extracellular traps suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on neutrophil extracellular traps inhibition as a novel therapeutic strategy. METHODS: Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for seven days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 hours. Immunofluorescence detected neutrophil extracellular traps, and Hematoxylin and Eosin staining assessed inflammatory cell. RESULTS: We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of neutrophil extracellular traps in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4(PAD-4) was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of neutrophil extracellular traps by inhibiting PAD-4. CONCLUSIONS: NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting neutrophil extracellular traps formation, with PAD-4 inhibition being one of its mechanisms.

Optimization Strategies of Na3V2(PO4)3 Cathode Materials for Sodium-Ion Batteries.

Na3V2(PO4)3 (NVP) has garnered great attentions as a prospective cathode material for sodium-ion batteries (SIBs) by virtue of its decent theoretical capacity, superior ion conductivity and high structural stability. However, the inherently poor electronic conductivity and sluggish sodium-ion diffusion kinetics of NVP material give rise to inferior rate performance and unsatisfactory energy density, which strictly confine its further application in SIBs. Thus, it is of significance to boost the sodium storage performance of NVP cathode material. Up to now, many methods have been developed to optimize the electrochemical performance of NVP cathode material. In this review, the latest advances in optimization strategies for improving the electrochemical performance of NVP cathode material are well summarized and discussed, including carbon coating or modification, foreign-ion doping or substitution and nanostructure and morphology design. The foreign-ion doping or substitution is highlighted, involving Na, V, and PO43- sites, which include single-site doping, multiple-site doping, single-ion doping, multiple-ion doping and so on. Furthermore, the challenges and prospects of high-performance NVP cathode material are also put forward. It is believed that this review can provide a useful reference for designing and developing high-performance NVP cathode material toward the large-scale application in SIBs.

Construction of a In2O3/ultrathin g-C3N4 S-scheme heterojunction for sensitive photoelectrochemical aptasensing of diazinon.

A single semiconductor-based photoelectrochemical (PEC) aptasensor usually faces a challenge of low sensitivity due to poor solar energy utilization and a high photogenerated carrier recombination rate. Herein, an ultra-thin carbon nitride nanosheet-coated In2O3 (In2O3/CNS) S-type heterojunction-based PEC aptasensor has been established to achieve highly sensitive detection of diazinon (DZN) pesticide in water environment. Construction of S-type heterojunction induces a band shift and an electric field effect, enhancing light utilization and accelerating directional transmission of carriers, leading to outstanding PEC performance. The creation of internal electric field at interface ensures stable carrier transport. Additionally, ultrathin CNS structure can effectively shorten the transport path of carriers. The close coating of In2O3 and CNS promotes the transfer of charge. The synergistic effects amplify the sensor's response, ultimately enabling the effective detection of DZN residue over a wide detection range (0.98 âˆ¼ 980.0 pg mL-1), a low detection limit (0.33 pg mL-1, S/N = 3) and excellent accuracy in practical application (RSD < 5 %). This work provides a reference for the construction of a new S-type heterojunction-based PEC sensor.

The effect of transcutaneous electrical acupoint stimulation on postoperative awakening after general anaesthesia: a systematic review and meta-analysis.

Background: The existing body of research concerning the impact of transcutaneous electrical acupoint stimulation (TEAS) on early postoperative recovery is marked by a lack of consensus. This meta-analysis, encompassing a systematic review of randomised controlled trials, seeks to critically assess the efficacy of TEAS in relation to awakening from general anaesthesia in the postoperative period. Methods: The inclusion criteria for this study were peer-reviewed randomised controlled trials that evaluated the influence of TEAS on the process of regaining consciousness following general anaesthesia. A comprehensive search was conducted across several reputable databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the VIP Database, the SinoMed Database, and the WANFANG Medical Database. The search was not limited by date, extending from the inception of each database up to December 2023. The methodological quality and risk of bias within the included studies were appraised in accordance with the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1, and its associated tool for assessing risk of bias. Results: The analysis encompassed 29 studies involving a total of 2,125 patients. Participants in the TEAS group demonstrated a significantly shorter duration to achieve eye-opening [mean difference (MD), -3.16 min; 95% confidence interval (CI), -3.93 to -2.39], endotracheal extubation (MD, -4.28 min; 95% CI, -4.79 to -3.76), and discharge from the post-anaesthesia care unit (MD, -8.04 min; 95% CI, -9.48 to -6.61) when compared to the control group receiving no or sham stimulation. Additionally, the TEAS group exhibited markedly reduced mean arterial blood pressure (MD, -9.00 mmHg; 95% CI, -10.69 to -7.32), heart rate (MD, -7.62 beats/min; 95% CI, -9.02 to -6.22), and plasma concentrations of epinephrine (standardised MD, -0.81; 95% CI, -1.04 to -0.58), norepinephrine (MD, -47.67 pg/ml; 95% CI, -62.88 to -32.46), and cortisol (MD, -110.92 nmol/L; 95% CI, -131.28 to -90.56) at the time of extubation. Furthermore, the incidence of adverse effects, including agitation and coughing, was considerably lower in the TEAS group relative to the control group (odds ratio, 0.30; 95% CI, 0.22-0.40). Conclusion: The findings of this study indicate that TEAS may hold promise in facilitating the return of consciousness, reducing the interval to awakening post-general anaesthesia, and enhancing the awakening process to be more tranquil and secure with a diminished likelihood of adverse events. However, caution must be exercised in interpreting these results due to the notable publication and geographical biases present among the studies under review. There is an imperative for further high-quality, low-bias research to substantiate these observations. Systematic review registration: The review protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42022382017).

Breaking through diabetes management barriers: Assessing the accuracy of Freestyle Libre Pro flash continuous glucose monitoring in diabetes patients with myocardial infarction.

Purpose: The objective of this study was to assess the accuracy of FreeStyle Libre Pro (FSL-Pro) flash continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods: A single-arm, single-center prospective study was conducted in the cardiac care unit from January 2021 to September 2023. Patients underwent finger-prick blood glucose (FPBG) testing before breakfast (6:00 am) and after meals (at 9:00, 13:00, 19:00 pm), along with CGM during their hospitalization. Statistical analyses included mean differences (MDs), mean absolute relative difference (MARDs) of blood glucose levels, and hypoglycemia occurrences. A Bland-Altman plot analysis and Pearson correlation were performed. Results: Ninety-seven T2DM and AMI patients underwent CGM for up to 72 h (1142 monitoring point). Mean daily BG, Fasting plasma glucose (FPG) and mean postprandial plasma glucose (PPG) were significantly lower by CGM than by FPBG with an estimated MD of -0.89 mmol/L in BG, -0.88 mmol/L in FPG, and -0.90 mmol/L in PPG, respectively. The maximum effect was mainly in the first day and then the difference was gradually declined (falling range, Day1, -1.24; Day 2, -0.70; Day 3, -0.68, mmol/L, respectively). The incidence rates of hypoglycemia and potential hypoglycemia was 1.57% and 8.5% higher, respectively, in CGM than in FBPG. A Bland-Altman Plot revealed some variability and bias between the two methods of measurement of glucose monitoring (p < .001). Pearson's correlation coefficient demonstrated a significant correlation between the mean BG, FPG, and PPG of CGM and FBPG (Pearson's coefficient: 0.92, 0.87, 0.92, respectively, p < .001). Conclusion: Compared with FPBG, FSL Pro-CGM showed lower mean glucose and higher hypoglycemia detection in T2DM and AMI patients, especially in the first 24 h.

Disability trajectories individuals with spinal cord injury in mainland China: do psychosocial resources and diseases factors predict trajectories?

STUDY DESIGN: Observational cohort study. OBJECTIVE: To identify classes of disability trajectories from 1 month post-injury (acute hospital) to 6 months post-injury (individuals with SCI individuals who stay in rehabilitation setting or back in the community), and to investigate whether psychosocial resources and disease factors can predict disability trajectory. SETTING: Spinal surgery in three Class III hospitals. Hospitals in China are divided into three classes (Class I, II and III). METHODS: All the participants were submitted to WHO Disability Assessment Schedule (WHO-DAS 2.0) at three times; and personal data anamnesis, level of hope, level of PTSD, level of social support were recorded at first time. All the data collected by the master's students who participated in this study. RESULTS: Two disability trajectories were identified using the latent class growth model: the continuous high disability group (N = 196, 93.3%) and the low starting point stabilization group (N = 14, 6.7%). Complete injury(ASIA-A) with SCI and more depression in the stable condition after SCI surgery were more likely to be classified as having higher disability than those with a lower disability trajectory. Occupation, annual family income, hope, social support, and Post-traumatic Stress Disorder (PTSD) cannot predict individuals belonging to trajectory classes. CONCLUSION: These findings emphasize the importance of ASIA and depression in the early recovery stage after SCI and support the opinion that strengthening psychological nursing and rehabilitation management at an early stage after SCI will benefit individuals with a lower disability trajectory.

FGF21 modulates immunometabolic homeostasis via the ALOX15/15-HETE axis in early liver graft injury.

Fibroblast growth factor 21 (FGF21) is essential for modulating hepatic homeostasis, but the impact of FGF21 on liver graft injury remains uncertain. Here, we show that high FGF21 levels in liver graft and serum are associated with improved graft function and survival in liver transplantation (LT) recipients. FGF21 deficiency aggravates early graft injury and activates arachidonic acid metabolism and regional inflammation in male mouse models of hepatic ischemia/reperfusion (I/R) injury and orthotopic LT. Mechanistically, FGF21 deficiency results in abnormal activation of the arachidonate 15-lipoxygenase (ALOX15)/15-hydroxy eicosatetraenoic acid (15-HETE) pathway, which triggers a cascade of innate immunity-dominated pro-inflammatory responses in grafts. Notably, the modulating role of FGF21/ALOX15/15-HETE pathway is more significant in steatotic livers. In contrast, pharmacological administration of recombinant FGF21 effectively protects against hepatic I/R injury. Overall, our study reveals the regulatory mechanism of FGF21 and offers insights into its potential clinical application in early liver graft injury after LT.

Deep bone oncology Diagnostics: Computed tomography based Machine learning for detection of bone tumors from breast cancer metastasis.

Purpose: The objective of this study is to develop a novel diagnostic tool using deep learning and radiomics to distinguish bone tumors on CT images as metastases from breast cancer. By providing a more accurate and reliable method for identifying metastatic bone tumors, this approach aims to significantly improve clinical decision-making and patient management in the context of breast cancer. Methods: This study utilized CT images of bone tumors from 178 patients, including 78 cases of breast cancer bone metastases and 100 cases of non-breast cancer bone metastases. The dataset was processed using the Medical Image Segmentation via Self-distilling TransUNet (MISSU) model for automated segmentation. Radiomics features were extracted from the segmented tumor regions using the Pyradiomics library, capturing various aspects of tumor phenotype. Feature selection was conducted using LASSO regression to identify the most predictive features. The model's performance was evaluated using ten-fold cross-validation, with metrics including accuracy, sensitivity, specificity, and the Dice similarity coefficient. Results: The developed radiomics model using the SVM algorithm achieved high discriminatory power, with an AUC of 0.936 on the training set and 0.953 on the test set. The model's performance metrics demonstrated strong accuracy, sensitivity, and specificity. Specifically, the accuracy was 0.864 for the training set and 0.853 for the test set. Sensitivity values were 0.838 and 0.789 for the training and test sets, respectively, while specificity values were 0.896 and 0.933 for the training and test sets, respectively. These results indicate that the SVM model effectively distinguishes between bone metastases originating from breast cancer and other origins. Additionally, the average Dice similarity coefficient for the automated segmentation was 0.915, demonstrating a high level of agreement with manual segmentations. Conclusion: This study demonstrates the potential of combining CT-based radiomics and deep learning for the accurate detection of bone metastases from breast cancer. The high-performance metrics indicate that this approach can significantly enhance diagnostic accuracy, aiding in early detection and improving patient outcomes. Future research should focus on validating these findings on larger datasets, integrating the model into clinical workflows, and exploring its use in personalized treatment planning.

A novel fluorescent sensor for evaluating pH changes in organophosphorus pesticides-treated cells and C. elegans.

pH plays an important role in the evaluation of the healthy status in versatile circumstances. The fluctuation of pH could be affected by complex internal and external stimuli. Especially, the abnormal pH changes is a common characteristic of organophosphorus pesticides (OPs)-caused damage owing to the irreversible inhibition of acetylcholinesterase (AChE) activity. Therefore, the rapid and efficient detection of pH changes is of great significance for predicting the OPs poisoning in living system. However, quick and convenient detecting pH levels in living cells is still limited by the lack of effective chemical tools. Here, a novel fluorescent probe TH-1 based on ESIPT mechanism was synthesized, showing specific fluorescent effects in different pH solutions. Importantly, the AChE catalyzed the hydrolysis product of acetylthiocholine iodide (ATCh) and changed the pH of solution, which influence its fluorescent intensity. Moreover, the probe TH-1 was applied to detecting the pH levels in living cells and C. elegans, providing an efficient chemical sensor for revealing the potential mechanisms of OPs in physiological and pathological processes.

Associations between cytokine levels and cognitive function among individuals at clinical high risk for psychosis.

OBJECTIVE: To explore the intricate interplay among cytokines, cognitive functioning, and conversion to psychosis in individuals at clinical high-risk (CHR) for psychosis. METHOD: We initially enrolled 385 individuals at CHR and 95 healthy controls (HCs). Subsequently, 102 participants at CHR completed the 1-year follow-up assessments, and 47 participants transitioned to psychosis. We assessed the levels of interleukins (IL-1ß, IL-2, IL-6, IL-8, IL-10), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). We comprehensively evaluated cognitive performance across six domains, including speed of processing (SP), attention/vigilance (AV), working memory (WM), verbal learning (VeL), visual learning (ViL), and reasoning and problem-solving (RPS). RESULTS: Higher baseline cognitive domain scores were associated with elevated GM-CSF and reduced VEGF levels. In the follow-up analysis, significant time effects were observed for IL-1ß and IL-2. We also observed significant interaction effects between specific cognitive domains (AV, WM, VeL, and OCS) and levels of cytokine (GM-CSF, IL-1ß, IL-6, and TNF-α). Changes in WM were negatively correlated with changes in TNF-α levels and positively correlated with changes in VEGF levels. Variations in VeL were inversely correlated with changes in GM-CSF and IL-10 levels, whereas changes in RPS were positively associated with changes in GM-CSF and IL-8 levels. CONCLUSIONS: Our results revealed intricate associations among cytokine levels, cognitive performance, and psychosis progression.

ß-synuclein regulates the phase transitions and amyloid conversion of α-synuclein.

Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. ß-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that ß-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated ß-synuclein mutations lose these capacities. Exogenous ß-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated ß-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/ß-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and ß-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.