Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

BACKGROUND: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. OBJECTIVE/METHODS: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. RESULTS: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. CONCLUSION: Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

Real-Time Monitoring of Multistep Batch and Flow Synthesis Processes of a Key Intermediate of Lifitegrast by a Combined Spectrometer System with Both Near-Infrared and Raman Spectroscopies Coupled to Partial Least-Squares.

Process analytical technology (PAT) has been successfully applied in numerous chemical synthesis cases and is an important tool in pharmaceutical process research and development. PAT brings new methods and opportunities for the real-time monitoring of chemical processes. In multistep synthesis, real-time monitoring of the complex reaction mixtures is a significant challenge but provides an opportunity to enhance reaction understanding and control. In this study, a combined multichannel spectrometer system with both near-infrared and Raman spectroscopy was built, and calibration models were developed to quantify the desired products, intermediates, and impurities in real-time at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating dynamic experiments in both batch and continuous-flow processes. It represents a significant step forward in data-driven, multistep pharmaceutical ingredient synthesis.

A nomogram for predicting cerebral white matter lesions in elderly men.

Objective: This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Methods: Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. Result: A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. Conclusion: We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery.

There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a pro-efferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.

Value of orthogonal axial MR images in preoperative T staging of gastric cancer.

PURPOSE: To assess the value of orthogonal axial images (OAI) of MRI in gastric cancer T staging. METHODS: This retrospective study enrolled 133 patients (median age, 63 [range, 24-85] years) with gastric adenocarcinoma who underwent both CT and MRI followed by surgery. MRI lacking or incorporating OAI and CT images were evaluated, respectively. Diagnostic performance (accuracy, sensitivity, and specificity) for each T stage, overall diagnostic accuracy and rates of over- and understaging were quantified employing pathological T stage as a reference standard. The McNemar's test was performed to compare the overall accuracy. RESULTS: Among patients with pT1-pT4 disease, MRI with OAI (accuracy: 88.7-94.7%, sensitivity: 66.7-93.0%, specificity: 91.5-100.0%) exhibited superior diagnostic performance compared to MRI without OAI (accuracy: 81.2-88.7%, sensitivity: 46.2-83.1%, specificity: 85.5-99.1%) and CT (accuracy: 88.0-92.5%, sensitivity: 53.3-90.1%, specificity: 88.7-98.1%). The overall accuracy of MRI with OAI was significantly higher (83.5%) than that of MRI without OAI (67.7%) (p < .001). However, there was no significant difference in the overall accuracy of MRI with OAI and CT (78.9%) (p = .35). The over- and understaging rates of MRI with OAI (12.0, 4.5%) were lower than those of MRI without OAI (21.8, 10.5%) and CT (12.8, 8.3%). CONCLUSION: OAI play a pivotal role in the T staging of gastric cancer. MRI incorporating OAI demonstrated commendable performance for gastric cancer T-staging, with a slight tendency toward its superiority over CT.

Droplet-based mechanical transducers modulated by the symmetry of wettability patterns.

Asymmetric mechanical transducers have important applications in energy harvesting, signal transmission, and micro-mechanics. To achieve asymmetric transformation of mechanical motion or energy, active robotic metamaterials, as well as materials with asymmetric microstructures or internal orientation, are usually employed. However, these strategies usually require continuous energy supplement and laborious fabrication, and limited transformation modes are achieved. Herein, utilizing wettability patterned surfaces for precise control of the droplet contact line and inner flow, we demonstrate a droplet-based mechanical transducer system, and achieve multimodal responses to specific vibrations. By virtue of the synergistic effect of surface tension and solid-liquid adhesion on the liquid dynamics, the droplet on the patterned substrate can exhibit symmetric/asymmetric vibration transformation when the substrate vibrates horizontally. Based on this, we construct arrayed patterns with distinct arrangements on the substrate, and employ the swarm effect of the arrayed droplets to achieve three-dimensional and multimodal actuation of the target plate under a fixed input vibration. Further, we demonstrate the utilization of the mechanical transducers for vibration management, object transport, and laser modulation. These findings provide a simple yet efficient strategy to realize a multimodal mechanical transducer, which shows significant potential for aseismic design, optical molding, as well as micro-electromechanical systems (MEMS).

A new combination and synonym in Bupleurum (Apiaceae, Apioideae), based on morphological, molecular and cytological evidence.

Specimen examinations and field observations revealed that Bupleurumsmithiivar.parvifolium was distinctly different from B.smithiivar.smithii in umbel, leaf, and fruit morphology, but was very similar to B.commelynoideumvar.flaviflorum. Based on these morphological evidences, the present study re-examined the taxonomic status of these taxa through morphological, cytological, and phylogenetic analyses. The results showed distinguishable features in the width of middle leaves and bracteoles of B.smithiivar.parvifolium compared to B.smithiivar.smithii. Morphological variation between B.smithiivar.parvifolium and B.commelynoideumvar.flaviflorum was continuous and overlapping. Notably, the chromosome number of B.smithiivar.parvifolium was 2n = 14 (x = 7), consistent with B.commelynoideumvar.flaviflorum, whereas B.smithiivar.smithii was 2n = 64 (x = 8). Additionally, phylogenetic analyses revealed B.commelynoideumvar.flaviflorum nested within B.smithiivar.parvifolium, and that both were distant from the B.smithiivar.smithii and B.commelynoideumvar.commelynoideum. Based on the evidence above, the differences between B.smithiivar.parvifolium and B.smithiivar.smithii extend beyond the level of intraspecific variation, and B.commelynoideumvar.flaviflorum is considered to be identical with B.smithiivar.parvifolium. Hence. A new combination and status, B.parvifolium (Shan & Y.Li) Q.R.Liu & L.H.Wang, comb. et stat. nov., is proposed. Furthermore, B.commelynoideumvar.flaviflorum should be treated as a synonym of B.parvifolium.

Electric field control of perpendicular magnetic tunnel junctions with easy-cone magnetic anisotropic free layers.

Magnetic tunnel junctions (MTJs) are the core element of spintronic devices. Currently, the mainstream writing operation of MTJs is based on electric current with high energy dissipation, and it can be notably reduced if an electric field is used instead. In this regard, it is promising for electric field control of MTJ in the multiferroic heterostructure composed of MTJ and ferroelectrics via strain-mediated magnetoelectric coupling. However, there are only reports on MTJs with in-plane anisotropy so far. Here, we investigate electric field control of the resistance state of MgO-based perpendicular MTJs with easy-cone anisotropic free layers through strain-mediated magnetoelectric coupling in multiferroic heterostructures. A remarkable, nonvolatile, and reversible modulation of resistance at room temperature is demonstrated. Through local reciprocal space mapping under different electric fields for Pb(Mg1/3Nb2/3)0.7Ti0.3O3 beneath the MTJ pillar, the modulation mechanism is deduced. Our work represents a crucial step toward electric field control of spintronic devices with non-in-plane magnetic anisotropy.

Copper-Catalyzed Enantioselective 1,2-Allylation of Azadienes with Allylboronates.

Catalytic asymmetric 1,2-allylation of aurone-derived azadienes is very difficult to achieve due to the driving force for aromatization and the greater steric hindrance of 1,2-addition compared with 1,4-addition. By taking advantage of the ability of nitrogen ligated metal complexes, we successfully demonstrated the first example of copper-catalyzed 1,2-allylation of azadienes with allylboronates for the highly enantioselective synthesis of homoallylic amines. Meanwhile, the enantioenriched 1,4-addition products could also be obtained through a subsequent 3,3-sigmatropic rearrangement of the 1,2-addition products. Extensive DFT calculations were carried out to elucidate the origins of high regioselectivity (1,2- vs 1,4-) and enantioselectivity.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

Bacitracin-resistant Staphylococcus aureus induced in chicken gut and in vitro under bacitracin exposure.

It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively.

A special type of homicide-suicide: A retrospective study of the characteristics of extended suicide.

Extended suicide, a specific type of homicide-suicide event, has severe social consequences yet remains lacking systematic research. This retrospective study investigated 51 cases of extended suicide involving mental disorders in central China with aim of better understanding risk factors for such events and guiding prevention strategies. Over an 8-year period from 2015 to 2022, cases were collected from forensic institutions, and demographic characteristics, case details, and psychiatric data were recorded. The 51 incidents involved 51 perpetrators and 79 victims, with more female perpetrators (58.8%) and more female victims (54.4%). The average age of the perpetrators was 36.1, and most were married (88.2%). Almost all of the victims were family members of the perpetrator, like the most numerous children (64.6%), followed by spouses (24.1%). The most common homicide mode of death was mechanical asphyxia (38.0%), followed by sharp devices (36.7%) and drug poisoning (16.5%). Depressive disorders (76.5%) were the most common diagnosis of mental disorder for perpetrators. The study analyzed the unique characteristics of extended suicide to enrich such data. These findings help strengthen the screening and identification of potential perpetrators and victims to prevent such cases from occurring.

Gliotoxin elicits immunotoxicity in the early innate immune system of ducks.

Gliotoxin (GT) belongs to the epipolythiodioxopiperazine (ETP) family, which is considered a crucial virulence determinant among the secondary metabolites produced by Aspergillus fumigatus. The metabolites are commonly found in food and feed, contributing to the invasion and immune escape of Aspergillus fumigatus, thereby posing a significant threat to the health of livestock, poultry, and humans. Heterophil extracellular traps (HETs), a novel form of innate immune defense, have been documented in the chicken's innate immune systems for capturing and eliminating invading microbes. However, the effects and mechanisms of GT on the production of duck HETs in vitro remain unknown. In this study, we first confirmed the presence of HETs in duck innate immune systems and further investigated the molecular mechanism underlying GT-induced HETs release. Our results demonstrate that GT can trigger typical release of HETs in duck. The structures of GT-induced HETs structures were characterized by DNA decoration, citrullinated histones 3, and elastase. Furthermore, NADPH oxidase, glycolysis, ERK1/2 and p38 signaling pathway were found to regulate GT-induced HETs. In summary, our findings reveal that gliotoxin activates HETs release in the early innate immune system of duck while providing new insights into the immunotoxicity of GT towards ducks.

The Prognostic Value of the Combination of the Prognostic Nutritional Index and the Lymphocyte:Monocyte Ratio for the Prediction of Patients with Muscle-Invasive Bladder Cancer.

OBJECTIVE: To explore the efficacy of combining the prognostic nutritional index (PNI) and the lymphocyte:monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC). METHODS: Of 172 patients who were diagnosed with MIBC in our hospital, 94 were eligible for the study. The clinical data of the 94 patients with MIBC were collected. The patients were divided according to the optimal cut-off values for the preoperative PNI and LMR into a low-PNI subgroup (PNI <44.15, 52 patients), a high-PNI subgroup (PNI ≥44.15, 42 patients), a low-LMR subgroup (LMR <2.98, 50 patients) and a high-LMR subgroup (LMR ≥2.98, 44 patients). The area under the receiver operating characteristic (ROC) curve (AUC) was used to analyse the efficacy of the PNI and the LMR in predicting the prognosis of patients with MIBC. Univariate and multivariate logistic regression analyses were performed to evaluate prognostic factors for patients with MIBC. Kaplan-Meier (K‒M) survival analysis was used for overall survival (OS) analysis to explore the ability of the PNI combined with the LMR to predict the prognosis of patients with MIBC. RESULTS: The optimal cut-off values for the preoperative PNI and the preoperative LMR were 44.15 and 2.98, respectively, on the basis of ROC curves. ROC curve analysis revealed that the PNI (AUC = 0.720, sensitivity 65.9%, specificity 74.50%, Youden index 0.399) and the LMR (AUC = 0.724, sensitivity 65.9%, specificity 70.0%, Youden index 0.395) both had good prognostic efficacy for patients with MIBC. The results of univariate and multivariate logistic regression analyses showed that preoperative PNI <44.15 was an independent risk factor for OS in patients with MIBC (p = 0.027). Based on K‒M survival curve analysis, patients with PNI <44.15 and LMR <2.98 had the shortest OS (p = 0.00002). CONCLUSIONS: Low preoperative PNI and LMR values are indicative of poor prognosis in patients with MIBC. The efficacy of their combination was better than that of the factors independently.

Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function.

Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs. In vitro cell experiments have demonstrated that CDC23 promotes the proliferation of myoblasts, as well as significantly positively regulating the differentiation of skeletal muscle satellite cells. In addition, Gene Set Enrichment Analysis (GSEA) revealed a significant downregulation of the cell cycle pathway during the differentiation process of skeletal muscle satellite cells. The protein-protein interaction (PPI) network showed a high degree of interaction between genes related to the cell cycle pathway and CDC23. Subsequently, in differentiated myocytes induced after overexpression of CDC23, the level of CDC23 exhibited a significant negative correlation with the expression of key factors in the cell cycle pathway, suggesting that CDC23 may be involved in the inhibition of the cell cycle signaling pathway in order to promote the differentiation process. In summary, we preliminarily determined the function of CDC23 with the aim of providing new insights into molecular regulation during porcine skeletal muscle development.

Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats.

This study investigated the effects of hydroxycitric acid tripotassium hydrate on right ventricular function, myocardial and pulmonary vascular remodeling in rats with pulmonary hypertension, and possible mechanisms. METHODS: Pulmonary hypertension was induced in male Sprague-Dawley rats by a single subcutaneous injection of monocrotaline or hypoxic chamber. In vivo, inflammatory cytokine (including TNF-α, IL-1ß, IL-6, and TGF-ß, the level of SOD) expression, superoxide dismutase and hydrogen peroxide levels, and p-IκBα and p65 expressions were detected. In vitro, pulmonary artery smooth muscle cell proliferation and migration, ROS production, and hypoxia-inducible factor-1 expression were also studied. RESULTS: Hydroxycitric acid tripotassium hydrate decreased right ventricular systolic pressure and reduced right ventricular fibrosis and pulmonary vascular remodeling in rats with two kinds of pulmonary hypertension. Moreover, the expression of both inflammatory and oxidative stress factors was effectively reduced, and the p65 signaling pathway was found to be inhibited in this study. Additionally, hydroxycitric acid tripotassium hydrate inhibited human pulmonary artery smooth cell proliferation and migration in vitro. CONCLUSIONS: This study shows that hydroxycitric acid tripotassium hydrate can alleviate pulmonary hypertension caused by hypoxia and monocycloline in rats, improve remodeling of the right ventricle and pulmonary artery, and inhibit pulmonary artery smooth muscle cell proliferation and migration. The protective effects may be achieved by regulating inflammation and oxidative stress through the p65 signaling pathway.

Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Recent H9N2 avian influenza virus lost hemagglutination activity due to a K141N substitution in hemagglutinin.

The H9N2 avian influenza virus (AIV) represents a significant risk to both the poultry industry and public health. Our surveillance efforts in China have revealed a growing trend of recent H9N2 AIV strains exhibiting a loss of hemagglutination activity at 37°C, posing challenges to detection and monitoring protocols. This study identified a single K141N substitution in the hemagglutinin (HA) glycoprotein as the culprit behind this diminished hemagglutination activity. The study evaluated the evolutionary dynamics of residue HA141 and studied the impact of the N141K substitution on aspects such as virus growth, thermostability, receptor-binding properties, and antigenic properties. Our findings indicate a polymorphism at residue 141, with the N variant becoming increasingly prevalent in recent Chinese H9N2 isolates. Although both wild-type and N141K mutant strains exclusively target α,2-6 sialic acid receptors, the N141K mutation notably impedes the virus's ability to bind to these receptors. Despite the mutation exerting minimal influence on viral titers, antigenicity, and pathogenicity in chicken embryos, it significantly enhances viral thermostability and reduces plaque size on Madin-Darby canine kidney (MDCK) cells. Additionally, the N141K mutation leads to decreased expression levels of HA protein in both MDCK cells and eggs. These findings highlight the critical role of the K141N substitution in altering the hemagglutination characteristics of recent H9N2 AIV strains under elevated temperatures. This emphasizes the need for ongoing surveillance and genetic analysis of circulating H9N2 AIV strains to develop effective control and prevention measures.IMPORTANCEThe H9N2 subtype of avian influenza virus (AIV) is currently the most prevalent low-pathogenicity AIV circulating in domestic poultry globally. Recently, there has been an emerging trend of H9N2 AIV strains acquiring increased affinity for human-type receptors and even losing their ability to bind to avian-type receptors, which raises concerns about their pandemic potential. In China, there has been a growing number of H9N2 AIV strains that have lost their ability to agglutinate chicken red blood cells, leading to false-negative results during surveillance efforts. In this study, we identified a K141N mutation in the HA protein of H9N2 AIV to be responsible for the loss of hemagglutination activity. This finding provides insight into the development of effective surveillance, prevention, and control strategies to mitigate the threat posed by H9N2 AIV to both animal and human health.

Celastrol inhibits oligodendrocyte and neuron ferroptosis to promote spinal cord injury recovery.

BACKGROUND: Spinal cord injury (SCI) is a traumatic injury to the central nervous system and can cause lipid peroxidation in the spinal cord. Ferroptosis, an iron-dependent programmed cell death, plays a key role in the pathophysiology progression of SCI. Celastrol, a widely used antioxidant drug, has potential therapeutic value for nervous system. PURPOSE: To investigate whether celastrol can be a reliable candidate for ferroptosis inhibitor and the molecular mechanism of celastrol in repairing SCI by inhibiting ferroptosis. METHODS: First, a rat SCI model was constructed, and the recovery of motor function was observed after treatment with celastrol. The regulatory effect of celastrol on ferroptosis pathway Nrf2-xCT-GPX4 was detected by Western blot and immunofluorescence. Finally, the ferroptosis model of neurons and oligodendrocytes was constructed in vitro to further verify the mechanism of inhibiting ferroptosis by celastrol. RESULTS: Our results demonstrated that celastrol promoted the recovery of spinal cord tissue and motor function in SCI rats. Further in vitro and in vivo studies showed that celastrol significantly inhibited ferroptosis in neurons and oligodendrocytes and reduced the accumulation of ROS. Finally, we found that celastrol could inhibit ferroptosis by up-regulating the Nrf2-xCT-GPX4 axis to repair SCI. CONCLUSION: Celastrol effectively inhibits ferroptosis after SCI by upregulating the Nrf2-xCT-GPX4 axis, reducing the production of lipid ROS, protecting the survival of neurons and oligodendrocytes, and improving the functional recovery.