Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy.

BACKGROUND: Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. SUBJECTIVE: The purpose of this study was to identify the potential lymph biomarkers for TIH. METHODS: Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. RESULTS: A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. CONCLUSIONS: This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.

Systematic evaluation of the meat qualities of free-range chicken (Xuan-Zhou) under different ages explored the optimal slaughter age.

Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age.

A down-regulated cytochrome P450 in Neoseiulus barkeri Hughes (Acari: Phytoseiidae) can dechlorinate and hydroxylate chlorpyrifos without producing chlorpyrifos-oxon.

Selection of chemical-resistant predatory mites is a good alternative to balance the contradiction between chemical control and biological control. Previously, a resistant strain of Neoseiulus barkeri for chlorpyrifos was obtained. In the current study, two up-regulated (NbCYP3A6, NbCYP3A16) and one down-regulated (NbCYP3A24) P450s were screened through differential expression analysis and other detoxification-related genes such as CCEs, GST, etc. were not found. 3D modelling and molecular docking indicated that the chlorine at position 5 on the pyridine ring of chlorpyrifos, as well as a methyl group, were closest to the heme iron of the enzymes (less than 5 Å). Three active recombinant P450 proteins were heterologously expressed and metabolized with chlorpyrifos in vitro. HPLC assay showed that only NbCYP3A24 could metabolize chlorpyrifos, with a metabolism rate of 21.60 %. Analysis of the m/z of metabolites by LC-MS/MS showed that chlorine at the 5C position of chlorpyrifos was stripped and hydroxylated, whereas chlorpyrifos-oxon, a common product of oxidation by P450, was not found. Knockdown of the NbCYP3A24 gene in the susceptiblestrain did reduce the susceptibility of N. barkeri to chlorpyrifos, suggesting that the biological activity of the metabolite may be similar to chlorpyrifos-oxon, thus enhancing the inhibitory effect on the target.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Development and validation of a diagnostic model for cerebral small vessel disease among rural older adults in China.

Objectives: Cerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults. Methods: This study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis. Results: The model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67-0.76) in the training set and 0.69 (95% CI, 0.63-0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50-90% in the training set, and 65-98% in the validation set. Conclusion: A model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

[Spatial distribution patterns and intraspecific and interspecific spatial associations of Quercus myrsinifolia population in Shennongjia, China]. / ç¥žå†œæž¶å°å¶é’å†ˆç§ç¾¤çš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† ç§é—´ç©ºé—´å ³è”.

Quercus myrsinifolia is one of the dominant species in the evergreen broad-leaf forest on the southern slope of Shennongjia. The study of spatial distribution pattern and spatial correlation of Q. myrsinifolia population will help to understand population development and potential ecological processes, as well as the structure and biodiversity maintenance mechanism of evergreen broad-leaf forests at the northern edge of the subtropics. Based on forest dynamic monitoring data from one 1 hm2 permanent plot on the southern slope of Shennongjia, we employed pair correlation functions g(r) and marked correlation functions to analyze the diameter structure of the Q. myrsinifolia population, spatial distribution patterns at different diameter classes, and intraspecific and interspecific spatial associations. The results showed that diameter structure of Q. myrsinifolia population exhibited an inverted 'J'-shaped distribution, suggesting a healthy regeneration status and belonging to a growing population type. The spatial distribution showed a decreasing trend in aggregation with increasing diameter. Positive correlations among individuals strengthened with closer diameter classes, while weakening with larger diameter differences. Interspecific spatial associations showed an increasing correlation of Q. myrsinifolia with understory dominant species with increasing spatial scales, but no correlation was observed with canopy-dominant species. Our results suggested that the spatial pattern of Q. myrsinifolia populations on the southern slope of Shennongjia was mainly influenced by habitat filtering, seed dispersal limitation, and intraspecific and interspecific competition. Furthermore, the adaptive strategies of Q. myrsinifolia varied when they coexisted with different species.

Evolving ω-amine transaminase AtATA guided by substrate-enzyme binding free energy for enhancing activity and stability against non-natural substrates.

In the field of chiral amine synthesis, ω-amine transaminase (ω-ATA) is one of the most established enzymes capable of asymmetric amination under optimal conditions. However, the applicability of ω-ATA toward more non-natural complex molecules remains limited due to its low transamination activity, thermostability, and narrow substrate scope. Here, by employing a combined approach of computational virtual screening strategy and combinatorial active-site saturation test/iterative saturation mutagenesis strategy, we have constructed the best variant M14C3-V5 (M14C3-V62A-V116S-E117I-L118I-V147F) with improved ω-ATA from Aspergillus terreus (AtATA) activity and thermostability toward non-natural substrate 1-acetylnaphthalene, which is the ketone precursor for producing the intermediate (R)-(+)-1-(1-naphthyl)ethylamine [(R)-NEA] of cinacalcet hydrochloride, showing activity enhancement of up to 3.4-fold compared to parent enzyme M14C3 (AtATA-F115L-M150C-H210N-M280C-V149A-L182F-L187F). The computational tools YASARA, Discovery Studio, Amber, and FoldX were applied for predicting mutation hotspots based on substrate-enzyme binding free energies and to show the possible mechanism with features related to AtATA structure, catalytic activity, and stability in silico analyses. M14C3-V5 achieved 71.8% conversion toward 50 mM 1-acetylnaphthalene in a 50 mL preparative-scale reaction for preparing (R)-NEA. Moreover, M14C3-V5 expanded the substrate scope toward aromatic ketone compounds. The generated virtual screening strategy based on the changes in binding free energies has successfully predicted the AtATA activity toward 1-acetylnaphthalene and related substrates. Together with experimental data, these approaches can serve as a gateway to explore desirable performances, expand enzyme-substrate scope, and accelerate biocatalysis.IMPORTANCEChiral amine is a crucial compound with many valuable applications. Their asymmetric synthesis employing ω-amine transaminases (ω-ATAs) is considered an attractive method. However, most ω-ATAs exhibit low activity and stability toward various non-natural substrates, which limits their industrial application. In this work, protein engineering strategy and computer-aided design are performed to evolve the activity and stability of ω-ATA from Aspergillus terreus toward non-natural substrates. After five rounds of mutations, the best variant, M14C3-V5, is obtained, showing better catalytic efficiency toward 1-acetylnaphthalene and higher thermostability than the original enzyme, M14C3. The robust combinational variant acquired displayed significant application value for pushing the asymmetric synthesis of aromatic chiral amines to a higher level.

Overexpression of a nuclear receptor HR96 contributes to spirodiclofen susceptibility in Panonychus citri (McGregor).

The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.

The placental blood perfusion and LINC00473-mediated promotion of trophoblast apoptosis in fetal growth restriction.

This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VIMV), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VIMV, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.

Case report: Bilateral facial palsy with paresthesias and positive anti-GT1a antibodies.

Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.

Rynchopeterine inhibits the formation of hypertrophic scars by regulating the miR-21/HIF1AN axis.

Hypertrophic scar (HS) is a fibroproliferative skin disease characterized by abnormal wound healing and pathological excessive fibrosis of the skin. Currently, the molecular mechanism of the disease is still largely unknown, and there is no effective drug treatment. In this study, we explored the effect of Rynchopeterine on the formation of HS. HS fibroblasts (HSFs) were isolated from the HS tissues of patients recovering from severe burns. After treating HSFs with different concentrations of Rynchopeterine, CCK-8, EdU, and Annexin V-FITC/PI assays were used to detect the proliferation, apoptosis, and contractile ability of HSFs. RT-qPCR and Western blotting were performed to evaluate the effect of Rynchopeterine on the expression of miR-21 and hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). The dual-luciferase reporter gene was used to verify the targeting relationship between miR-21 and HIF1AN. Rynchopeterine reduced the expression of Col1a2, Col3a1, and α-SMA, inhibited proliferation and contraction of HSFs, and increased apoptosis in a dose-dependent manner. miR-21 was highly expressed in HS tissues and HSFs, and Rynchopeterine could inhibit miR-21 expression. Overexpression of miR-21 and knockdown of HIF1AN increased proliferation, activation, contraction, and collagen synthesis of HSFs, and inhibited their apoptosis. In vivo, Rynchopeterine could reduce the collagen content of the dermis and the positive ratio of PCNA and α-SMA. Rynchopeterine is a good therapeutic agent for HS, which up-regulates the expression of HIF1AN by inhibiting miR-21, thereby inhibiting the formation of HS.

Study on the influence of water saturation on radon exhalation rates of rocks.

The radon exhalation characteristics of rocks will change significantly during water saturation treatment, and radon, as an important tracer, is of great significance in predicting rock activities. In this paper, the radon exhalation characteristics of rocks after saturated with different water contents were studied by centrifugal test, radon measurement test and other indoor tests. The results show that the radon exhalation rate of rocks shows a rising and then decreasing trend with the increase of rock water saturation. The radon precipitation rate peaked at 0.7 Sw âˆ¼ 0.8 Sw, and the high water saturation had an obvious inhibiting effect on the radon exhalation rate of rocks. The research results are of great significance in predicting the rock-water-based geological processes.

The lifestyle for brain health index, the cluster of differentiation 33 (CD33) gene, and cognitive function among rural Chinese older adults: A population-based study.

BACKGROUND: We sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. METHODS: This population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33(rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. RESULTS: A higher LIBRA index was associated with multivariable-adjusted ß-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33(rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: ß-coefficient=0.042; 95 %CI=0.008-0.077), the dominant (CA+AA vs. CC: 0.040; 0.007-0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009-0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (Pinteraction<0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). CONCLUSIONS: This population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association.

Association of objective sleep duration with cognition and brain aging biomarkers in older adults.

The neuropathological mechanisms underlying the association between sleep duration and mild cognitive impairment remain poorly understood. This population-based study included 2032 dementia-free people (age ≥ 60 years; 55.1% women) derived from participants in the Multimodal Interventions to Delay Dementia and Disability in Rural China; of these, data were available in 841 participants for Alzheimer's plasma biomarkers (e.g. amyloid-ß, total tau and neurofilament light chain), 1044 for serum microvascular biomarkers (e.g. soluble adhesion molecules) and 834 for brain MRI biomarkers (e.g. whiter matter, grey matter, hippocampus, lacunes, enlarged perivascular spaces and white matter hyperintensity WMH). We used electrocardiogram-based cardiopulmonary coupling analysis to measure sleep duration, a neuropsychological test battery to assess cognitive function and the Petersen's criteria to define mild cognitive impairment. Data were analysed with multivariable logistic and general linear models. In the total sample (n = 2032), 510 participants were defined with mild cognitive impairment, including 438 with amnestic mild cognitive impairment and 72 with non-amnestic mild cognitive impairment. Long sleep duration (>8 versus 6-8 h) was significantly associated with increased likelihoods of mild cognitive impairment and non-amnestic mild cognitive impairment and lower scores in global cognition, verbal fluency, attention and executive function (Bonferroni-corrected P < 0.05). In the subsamples, long sleep duration was associated with higher plasma amyloid-ß40 and total tau, a lower amyloid-ß42/amyloid-ß40 ratio and smaller grey matter volume (Bonferroni-corrected P < 0.05). Sleep duration was not significantly associated with serum-soluble adhesion molecules, white matter hyperintensity volume, global enlarged perivascular spaces and lacunes (P > 0.05). Alzheimer's and neurodegenerative pathologies may represent common pathways linking long sleep duration with mild cognitive impairment and low cognition in older adults.

Evaluation of the rapid Idylla IDH1-2 mutation assay in FFPE glioma samples.

IDH1 and IDH2 mutational status is a critical biomarker with diagnostic, prognostic, and treatment implications in glioma. Although IDH1 p.R132H-specific immunohistochemistry is available, it is unable to identify other mutations in IDH1/2. Next-generation sequencing can accurately determine IDH1/2 mutational status but suffers from long turnaround time when urgent treatment planning and initiation is medically necessary. The Idylla assay can detect IDH1/2 mutational status from unstained formalin-fixed paraffin-embedded (FFPE) slides in as little as a few hours. In a clinical validation, we demonstrate clinical accuracy of 97% compared to next-generation sequencing. Sensitivity studies demonstrated a limit of detection of 2.5-5% variant allele frequency, even at DNA inputs below the manufacturer's recommended threshold. Overall, the assay is an effective and accurate method for rapid determination of IDH1/2 mutational status.

A UDP-glycosyltransferase gene PcUGT202A9 was associated with abamectin resistance in Panonychus citri (McGregor).

Panonychus citri (McGregor) strains have developed a high level of resistance to abamectin, but the underlying molecular mechanism is unknown. Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are critical for the removal of a variety of exogenous and endogenous substances. In this study, an enzyme activity assay revealed that UGTs potentially contribute to P. citri abamectin resistance. Spatiotemporal expression profiles showed that only PcUGT202A9 was significantly overexpressed in the abamectin-resistant strain (AbR) at all developmental stages. Moreover, UGT activity decreased significantly, whereas abamectin susceptibility increased significantly, in AbR after PcUGT202A9 was silenced. Three-dimensional modeling and molecular docking analyses revealed that PcUGT202A9 can bind stably to abamectin. Recombinant PcUGT202A9 activity was detected when α-naphthol was used, but the enzymatic activity was inhibited by abamectin (50 % inhibitory concentration: 803.3 ±â€¯14.20 µmol/L). High-performance liquid chromatography and mass spectrometry analyses indicated that recombinant PcUGT202A9 can effectively degrade abamectin and catalyze the conjugation of UDP-glucose to abamectin. These results imply PcUGT202A9 contributes to P. citri abamectin resistance.

Discovery and validation of molecular patterns and immune characteristics in the peripheral blood of ischemic stroke patients.

Background: Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells. Methods: We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves. Results: We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set. Conclusion: Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS.

Burdock miR8175 in diet improves insulin resistance induced by obesity in mice through food absorption.

The incidence of type 2 diabetes mellitus (T2DM) induced by obesity is rapidly increasing. Although there are many synthetic drugs for treating T2DM, they have various side effects. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. After administration of burdock decoction or synthetic miR8175 by gavage, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting Ptprf and Ptp1b, which may be the reason for the improvement in metabolism. This study provides a theoretical basis for the main active component and molecular mechanism of burdock to improve insulin resistance. And the study also suggests that plant miRNA may be an indispensable nutrient for maintaining human health.

Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.