Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos.

Interphase chromatin is organized in distinct nuclear sub-compartments, reflecting its degree of compaction and transcriptional status. In Caenorhabditis elegans embryos, H3K9 methylation is necessary to silence and to anchor repeat-rich heterochromatin at the nuclear periphery. In a screen for perinuclear anchors of heterochromatin, we identified a previously uncharacterized C. elegans chromodomain protein, CEC-4. CEC-4 binds preferentially mono-, di-, or tri-methylated H3K9 and localizes at the nuclear envelope independently of H3K9 methylation and nuclear lamin. CEC-4 is necessary for endogenous heterochromatin anchoring, but not for transcriptional repression, in contrast to other known H3K9 methyl-binders in worms, which mediate gene repression but not perinuclear anchoring. When we ectopically induce a muscle differentiation program in embryos, cec-4 mutants fail to commit fully to muscle cell fate. This suggests that perinuclear sequestration of chromatin during development helps restrict cell differentiation programs by stabilizing commitment to a specific cell fate. PAPERCLIP.

The Salmonella Typhimurium Effector SpvB Subverts Host Membrane Trafficking by Targeting Clathrin and AP-1.

Salmonella enterica, the etiological agent of gastrointestinal and systemic diseases, translocates a plethora of virulence factors through its type III secretion systems to host cells during infection. Among them, SpvB has been reported to harbor an ADP-ribosyltransferase domain in its C terminus, which destabilizes host cytoskeleton by modifying actin. However, whether this effector targets other host factors as well as the function of its N terminus still remains to be determined. Here, we found that SpvB targets clathrin and its adaptor AP-1 (adaptor protein 1) via interactions with its N-terminal domain. Notably, our data suggest that SpvB-clathrin/AP-1 associations disrupt clathrin-mediated endocytosis and protein secretion pathway as well. In addition, knocking down of AP-1 promotes Salmonella intracellular survival and proliferation in host cells.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Causal Associations of Genetically Determined Tinnitus With Neuroimaging Traits: Evidence From a Mendelian Randomization Study.

OBJECTIVES: Potential reverse causality and unmeasured confounding factors are common biases in most neuroimaging studies on tinnitus and central correlates. The causal association of tinnitus with neuroimaging features also remains unclear. This study aimed to investigate the causal relationship of tinnitus with neuroplastic alterations using Mendelian randomization. DESIGN: Summary-level data from a genome-wide association study of tinnitus were derived from UK Biobank (n = 117,882). The genome-wide association study summary statistics for 4 global-brain tissue and 14 sub-brain gray matter volumetric traits were also obtained (n = up to 33,224). A bidirectional Mendelian randomization analysis was conducted to explore the causal relationship between tinnitus and neuroanatomical features at global-brain and sub-brain levels. RESULTS: Genetic susceptibility to tinnitus was causally associated with increased white matter volume (odds ratio [OR] = 2.361, 95% confidence interval [CI], 1.033 to 5.393) and total brain volume (OR = 2.391, 95% CI, 1.047 to 5.463) but inversely associated with cerebrospinal fluid volume (OR = 0.362, 95% CI, 0.158 to 0.826). A smaller gray matter volume in the left Heschl's gyrus and right insular cortex and larger gray matter volume in the posterior division of the left parahippocampal gyrus may lead to an increased risk for tinnitus (OR = 0.978, 95% CI, 0.961 to 0.996; OR = 0.987, 95% CI, 0.976 to 0.998; and OR = 1.015, 95% CI, 1.001 to 1.028, respectively). CONCLUSIONS: Genetic susceptibility to tinnitus was causally associated with increased white matter volume and total brain volume. Volume alteration in several cortical regions may indicate a higher tinnitus risk, and further research is recommended for causality inference at the level of sub-brain regions. Our findings provide genetic evidence for elucidating the underlying pathophysiological mechanisms of tinnitus-related neuroanatomical abnormalities.

A multi-Task Learning based applicable AI model simultaneously predicts stage, histology, grade and LNM for cervical cancer before surgery.

PURPOSE: To build an Mult-Task Learning (MTL) based Artificial Intelligence(AI) model that can simultaneously predict clinical stage, histology, grade and LNM for cervical cancer before surgery. METHODS: This retrospective and prospective cohort study was conducted from January 2001 to March 2014 for the training set and from January 2018 to November 2021 for the validation set at Beijing Chaoyang Hospital, Capital Medical University. Preoperative clinical information of cervical cancer patients was used. An Artificial Neural Network (ANN) algorithm was used to build the MTL-based AI model. Accuracy and weighted F1 scores were calculated as evaluation indicators. The performance of the MTL model was compared with Single-Task Learning (STL) models. Additionally, a Turing test was performed by 20 gynecologists and compared with this AI model. RESULTS: A total of 223 cervical cancer cases were retrospectively enrolled into the training set, and 58 cases were prospectively collected as independent validation set. The accuracy of this cervical cancer AI model constructed with ANN algorithm in predicting stage, histology, grade and LNM were 75%, 95%, 86% and 76%, respectively. And the corresponding weighted F1 score were 70%, 94%, 86%, and 76%, respectively. The average time consumption of AI simultaneously predicting stage, histology, grade and LNM for cervical cancer was 0.01s (95%CI: 0.01-0.01) per 20 patients. The mean time consumption doctor and doctor with AI were 581.1s (95%CI: 300.0-900.0) per 20 patients and 534.8s (95%CI: 255.0-720.0) per 20 patients, respectively. Except for LNM, both the accuracy and F-score of the AI model were significantly better than STL AI, doctors and AI-assisted doctors in predicting stage, grade and histology. (P < 0.05) The time consumption of AI was significantly less than that of doctors' prediction and AI-assisted doctors' results. (P < 0.05 CONCLUSION: A multi-task learning AI model can simultaneously predict stage, histology, grade, and LNM for cervical cancer preoperatively with minimal time consumption. To improve the conditions and use of the beneficiaries, the model should be integrated into routine clinical workflows, offering a decision-support tool for gynecologists. Future studies should focus on refining the model for broader clinical applications, increasing the diversity of the training datasets, and enhancing its adaptability to various clinical settings. Additionally, continuous feedback from clinical practice should be incorporated to ensure the model's accuracy and reliability, ultimately improving personalized patient care and treatment outcomes.

Different ethanol exposure durations affect cytochrome P450 2E1-mediated sevoflurane metabolism in rat liver.

BACKGROUND: Chronic alcohol users often exhibit an increased minimum alveolar concentration (MAC) of sevoflurane, yet the specific mechanism remains unclear. It has been reported that ethanol exposure can upregulate the protein expression and enzyme activity of cytochrome P450 2E1 (CYP2E1). CYP2E1 is a key enzyme that converts 2-5% of sevoflurane into equimolar amounts of hexafluoroisopropanol (HFIP) and F-. This study aims to explore whether ethanol exposure could alter sevoflurane metabolism through CYP2E1 modulation, potentially explaining the increased MAC observed in alcohol users. METHODS: Eighty adult male Sprague-Dawley (SD) rats were randomly divided into two groups and received either 50% ethanol (dose: 3 g/kg) or 0.9% saline twice daily by gavage. After 1, 2, 3, and 4 weeks of gavage, ten rats were randomly selected from each group to undergo 1-hour anesthesia with 2.3% sevoflurane. Blood samples were collected after anesthesia to measure the concentration of free HFIP using gas chromatography. Additionally, the left lobe tissue of the liver was collected for the analysis of CYP2E1 protein expression by Western blot and CYP2E1 enzyme activity by colorimetric assay. Correlations between these parameters were analyzed using Pearson's correlation. RESULTS: In the ethanol group, CYP2E1 expression, activity, and the concentration of free HFIP were significantly higher at all time points compared to the control group (P < 0.05), except for protein expression in the first week (P > 0.05). Within-group comparisons indicated no significant changes in any of the parameters for the control group (P > 0.05). In the ethanol group, there was no difference in free HFIP concentration between the first and second weeks (P > 0.05), but a significant increase was observed in the third and fourth weeks (P < 0.01); protein expression and enzyme activity significantly varied over time, especially showing a notable increase from the first to the third and fourth weeks (P < 0.05). Correlation analysis revealed strong positive correlations between free HFIP concentration and CYP2E1 activity (r = 0.7898), free HFIP concentration and CYP2E1 expression (r = 0.8418), and CYP2E1 activity and expression (r = 0.8740), all with P < 0.001. CONCLUSIONS: Ethanol exposure increased both the expression and enzymatic activity of CYP2E1, consequently enhancing the metabolism of sevoflurane.

Surviving winter on the Qinghai-Tibetan Plateau: Pikas suppress energy demands and exploit yak feces to survive winter.

The Qinghai-Tibetan Plateau, with low precipitation, low oxygen partial pressure, and temperatures routinely dropping below -30 °C in winter, presents several physiological challenges to its fauna. Yet it is home to many endemic mammalian species, including the plateau pika (Ochotona curzoniae). How these small animals that are incapable of hibernation survive the winter is an enigma. Measurements of daily energy expenditure (DEE) using the doubly labeled water method show that pikas suppress their DEE during winter. At the same body weight, pikas in winter expend 29.7% less than in summer, despite ambient temperatures being approximately 25 °C lower. Combined with resting metabolic rates (RMRs), this gives them an exceptionally low metabolic scope in winter (DEE/RMRt = 1.60 ± 0.30; RMRt is resting metabolic rate at thermoneutrality). Using implanted body temperature loggers and filming in the wild, we show that this is achieved by reducing body temperature and physical activity. Thyroid hormone (T3 and T4) measurements indicate this metabolic suppression is probably mediated via the thyroid axis. Winter activity was lower at sites where domestic yak (Bos grunniens) densities were higher. Pikas supplement their food intake at these sites by eating yak feces, demonstrated by direct observation, identification of yak DNA in pika stomach contents, and greater convergence in the yak/pika microbiotas in winter. This interspecific coprophagy allows pikas to thrive where yak are abundant and partially explains why pika densities are higher where domestic yak, their supposed direct competitors for food, are more abundant.

Optimization of Operational Parameters of Plant Protection UAV.

The operational parameters of plant protection unmanned aerial vehicles (UAVs) significantly impact spraying effectiveness, but the underlying mechanism remains unclear. This paper conducted a full factorial experiment with varying flight speeds, heights, and nozzle flow rates to collect parameter space data. Using the Kriging surrogate model, we characterized this parameter space and subsequently optimized the average deposition rate and coefficient of variation by employing a variable crossover (mutation) probability multi-objective genetic algorithm. In the obtained Pareto front, the average sedimentation rate is no less than 46%, with a maximum of 56.08%, and the CV coefficient is no more than 13.91%, with a minimum of only 8.42%. These optimized parameters enhance both the average deposition rate and spraying uniformity compared to experimental data. By employing these optimized parameters in practical applications, a balance between the maximum average deposition rate and minimum coefficient of variation can be achieved during UAV spraying, thereby reducing pesticide usage, promoting sustainable agriculture, and mitigating instances of missed spraying and re-spraying.

Optical Encryption in the Photonic Orbital Angular Momentum Dimension via Direct-Laser-Writing 3D Chiral Metahelices.

Vortex beams, which intrinsically possess optical orbital angular momentum (OAM), are considered as one of the promising chiral light waves for classical optical communications and quantum information processing. For a long time, it has been an expectation to utilize artificial three-dimensional (3D) chiral metamaterials to manipulate the transmission of vortex beams for practical optical display applications. Here, we demonstrate the concept of selective transmission management of vortex beams with opposite OAM modes assisted by the designed 3D chiral metahelices. Utilizing the integrated array of the metahelices, a series of optical operations, including display, hiding, and even encryption, can be realized by the parallel processing of multiple vortex beams. The results open up an intriguing route for metamaterial-dominated optical OAM processing, which fosters the development of photonic angular momentum engineering and high-security optical encryption.

Neutrophil extracellular trap-associated carbamylation and histones trigger osteoclast formation in rheumatoid arthritis.

OBJECTIVE: Neutrophil infiltration into the synovial joint is a hallmark of rheumatoid arthritis (RA), a disease characterised by progressive bone erosion. However, the mechanisms by which neutrophils participate in bone destruction remain unclear. Carbamylation is a posttranslational modification linked to increased bone erosion in RA and we previously showed that carbamylation is present in RA neutrophil extracellular traps (NETs). However, it remains unclear whether NETs and their carbamylated protein cargo directly promote bone destruction and alter osteoclast biology. METHODS: NETs and carbamylated NETs (cNETs) were assessed for their capacity to induce osteoclast formation in CD14+ monocytes. Chemical inhibitors and neutralising antibodies were used to elucidate the pathway by which NETs induce osteoclastogenesis. HLA-DRB1*04:01 mice received intra-articular injection of cNETs for 4 weeks. Joints were isolated and assessed for osteoclast formation. Plasma and synovial fluid samples from patients with RA (n=32) were assessed for the presence of carbamylated histone, and correlations to disease specific outcomes were performed. RESULTS: We found that NETs, when cNETs, instruct monocytes to undergo rapid osteoclast formation. NET-mediated osteoclastogenesis appears to depend on Toll-like receptor 4 signalling and NET-associated proteins including histones and neutrophil elastase. In vivo, we identified that the number of osteoclasts increased following immunisation with cNETs in HLA-DRB1*04:01 transgenic mice. Furthermore, carbamylated histones are increased in plasma and synovial fluid from patients with RA and correlate with active bone resorption and inflammatory markers. CONCLUSIONS: Our results suggest that NETs have a direct role in RA-associated bone erosion by promoting osteoclast formation.

Roles of Natural Phenolic Compounds in Polycyclic Aromatic Hydrocarbons Abiotic Attenuation at Soil-Air Interfaces through Oxidative Coupling Reactions.

Little information is available on the roles of natural phenolic compounds in polycyclic aromatic hydrocarbons (PAHs) attenuation at dry soil-air interfaces. The purpose of this study was to determine the roles of model phenolic constituents of soil organic matter (SOM) on the abiotic attenuation of PAHs. The phenolic compounds can significantly change the attenuation rates of PAHs, among which hydroquinone was the most effective in promoting anthracene and benzo[a]anthracene attenuation. Product identification and sequential extraction experiments revealed hydroquinone enhanced the formation of oxidative coupling products and promoted the incorporation of PAHs into humic analogues, thereby reducing potential risks to humans and ecosystems. Electron paramagnetic resonance spectroscopy analyses showed both PAHs and phenolic compounds could donate electrons to Lewis acid sites of soil minerals, resulting in the generation of persistent free radicals (PFRs). PFRs could promote the generation of ·OH to enhance PAH oxidation and could cross-couple with PAHs, resulting in high-molecular-weight oxidative coupling products. This study revealed for the first time the reaction mechanism between PAHs and phenolic components of SOM under relatively dry conditions and provided new insights into promoting PAHs detoxification in soils but also a potential strategy to increase the organic carbon sequestration.

MASI: microbiota-active substance interactions database.

Xenobiotic and host active substances interact with gut microbiota to influence human health and therapeutics. Dietary, pharmaceutical, herbal and environmental substances are modified by microbiota with altered bioavailabilities, bioactivities and toxic effects. Xenobiotics also affect microbiota with health implications. Knowledge of these microbiota and active substance interactions is important for understanding microbiota-regulated functions and therapeutics. Established microbiota databases provide useful information about the microbiota-disease associations, diet and drug interventions, and microbiota modulation of drugs. However, there is insufficient information on the active substances modified by microbiota and the abundance of gut bacteria in humans. Only ∼7% drugs are covered by the established databases. To complement these databases, we developed MASI, Microbiota-Active Substance Interactions database, for providing the information about the microbiota alteration of various substances, substance alteration of microbiota, and the abundance of gut bacteria in humans. These include 1,051 pharmaceutical, 103 dietary, 119 herbal, 46 probiotic, 142 environmental substances interacting with 806 microbiota species linked to 56 diseases and 784 microbiota-disease associations. MASI covers 11 215 bacteria-pharmaceutical, 914 bacteria-herbal, 309 bacteria-dietary, 753 bacteria-environmental substance interactions and the abundance profiles of 259 bacteria species in 3465 patients and 5334 healthy individuals. MASI is freely accessible at http://www.aiddlab.com/MASI.

Interferon lambda promotes immune dysregulation and tissue inflammation in TLR7-induced lupus.

Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such as systemic lupus erythematosus (SLE), a condition characterized by aberrant type I IFN signaling, has not been determined. Here, we identify a nonredundant role for IFN-λ in immune dysregulation and tissue inflammation in a model of TLR7-induced lupus. IFN-λ protein is increased in murine lupus and IFN-λ receptor (Ifnlr1) deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys without effects on autoantibody production. Single-cell RNA sequencing in mouse spleen and human peripheral blood revealed that only mouse neutrophils and human B cells are directly responsive to this cytokine. Rather, IFN-λ activates keratinocytes and mesangial cells to produce chemokines that induce immune cell recruitment and promote tissue inflammation. These data provide insights into the immunobiology of SLE and identify type III IFNs as important factors for tissue-specific pathology in this disease.

Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism.

Differences between female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. We previously reported that neutrophils from reproductive-age males are more immature and less activated than their female counterparts. To further characterize the mechanisms that drive differential neutrophil phenotypes, we performed RNA sequencing on circulating neutrophils from healthy adult females and males. Female neutrophils displayed significant up-regulation of type I IFN (IFN)-stimulated genes (ISGs). Single-cell RNA-sequencing analysis indicated that these differences are neutrophil specific, driven by a distinct neutrophil subset and related to maturation status. Neutrophil hyperresponsiveness to type I IFNs promoted enhanced responses to Toll-like receptor agonists. Neutrophils from young adult males had significantly increased mitochondrial metabolism compared to those from females and this was modulated by estradiol. Assessment of ISGs and neutrophil maturation genes in Klinefelter syndrome (47, XXY) males and in prepubescent children supported that differences in neutrophil phenotype between adult male and female neutrophils are hormonally driven and not explained by X chromosome gene dosage. Our results indicate that there are distinct sex differences in neutrophil biology related to responses to type I IFNs, immunometabolism, and maturation status that may have prominent functional and pathogenic implications.

Aging Characteristics and Ecological Effects of Primary Microplastics in Cosmetic Products Under Different Aging Processes.

Microplastics are becoming an increasingly environmental concern, but only a few studies have focused on primary microplastics. Herein, four primary microplastics (Lapis, Jade, Topaz and White) commonly used in cosmetic products were selected to investigate the effects of sunlight, seawater, and soil aging on their environmental behaviors. After sunlight and seawater aging, the surfaces of all four microplastics developed breaks and cracks, with particle sizes decreased and specific surface areas increased. Topaz exhibited the most significant changes under sunlight and seawater aging and its maximum adsorption capacity of phenanthrene significantly increased by 22.50% and 47.86%, respectively. Under soil aging, amending with either White or Topaz changed the soil bacterial community composition and diversity, but they had less ecological impacts than polyvinyl chloride plastic. The results of this study provide vital information for understanding the aging characteristics, environmental behavior, and ecological effects of primary microplastics under natural aging processes.

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. CONCLUSION: PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. TRIAL REGISTRATION NUMBER: NCT02338999.

Accurate droplet depth displacement measurement with time-resolved astigmatic interferometric particle imaging.

The astigmatic interferometric particle imaging (AIPI) model reveals that the fringe orientation shifts with droplet depth displacement, and their relationships are quantitatively formulated. The depth displacement is directly evaluated from the relative angular shift of the fringes with angular cross power spectral density, and this algorithm isolates the uncertainty of droplet depth position from depth displacement. Proof-of-concept experiments on micrometer-sized transparent droplets with a 5 kHz AIPI system demonstrates that droplet three-dimensional (3D) trajectories are accurately obtained with the accuracy of depth displacement up to tens of micrometers, improving an order of magnitude from hundreds of microns in a traditional Lagrangian framework by comparing droplet depth positions.

Mechanistic Study of the Effects of Agricultural Amendments on Photochemical Processes in Paddy Water during Rice Growth.

The photochemical properties of paddy water might be affected by the commonly used amendments in rice fields owing to the associated changes in water chemistry; however, this important aspect has rarely been explored. We examined the effects of agricultural amendments on the photochemistry of paddy water during rice growth. The amendments significantly influenced the photogenerated reactive intermediates (RIs) in paddy water, such as triplet dissolved organic matter (3DOM*), singlet oxygen, and hydroxyl radicals. Compared with control experiments without amendments, the application of straw and lime increased the RI concentrations by up to 16.8 and 11.1 times, respectively, while biochar addition had limited effects on RI generation from paddy water in in situ experiments under sunlight. Fluorescence emission-excitation matrix spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry, and structural equation modeling revealed that upon the addition of straw and lime amendments, humified DOM substances contained lignins, proteins, and fulvic acids, which could produce more RIs under irradiation. Moreover, the amendments significantly accelerated the degradation rate of 2,4-dichlorophenol but led to the 3DOM*-mediated formation of more toxic and stable dimeric products. This study provides new insights into the effects of amendments on the photochemistry of paddy water and the pathways of abiotic degradation of organic contaminants in paddy fields.

Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus.

Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined. Transcriptomics and epigenetic assessment of lupus LDGs, autologous normal-density neutrophils, and healthy control neutrophils was performed by bulk and single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. Functional readouts were compared among neutrophil subsets. SLE LDGs display significant transcriptional and epigenetic heterogeneity and comprise 2 subpopulations of intermediate-mature and immature neutrophils, with different degrees of chromatin accessibility and differences in transcription factor motif analysis. Differences in neutrophil extracellular trap (NET) formation, oxidized mitochondrial DNA release, chemotaxis, phagocytosis, degranulation, ability to harm the endothelium, and responses to type I interferon (IFN) stimulation are evident among LDG subsets. Compared with other immune cell subsets, LDGs display the highest expression of IFN-inducible genes. Distinct LDG subsets correlate with specific clinical features of lupus and with the presence and severity of coronary artery disease. Phenotypic, functional, and pathogenic neutrophil heterogeneity are prevalent in SLE and may promote immune dysregulation and prominent vascular damage characteristic of this disease.

PET-CT radiomics by integrating primary tumor and peritumoral areas predicts E-cadherin expression and correlates with pelvic lymph node metastasis in early-stage cervical cancer.

OBJECTIVES: To explore the role of radiomics in integrating primary tumor and peritumoral areas based on PET-CT scans for predicting E-cadherin (E-cad) expression in early-stage cervical cancer (ESCC) and its correlation with pelvic lymph node metastasis (PLNM). METHODS: Ninety-seven ESCC patients who had undergone PET-CT scans were retrospectively analyzed. The ROI of primary tumors, peritumoral areas, and plus tumors were semi-automatically segmented on PET-CT images. A total of 1188 radiomics features were extracted, selected, and eventually integrated into radiomics score (rad-score). The rad-score difference between patients with E-cad expression of high and low was analyzed using Mann-Whitney tests. Characteristic correlation was tested using a Spearman analysis. Four models were established using logistic regression algorithms and evaluated using ROC and calibration curves. A DeLong test was used to perform pairwise comparisons of AUCs. RESULTS: The rad-score of patients with low E-cad expression was higher than that of patients with high E-cad expression in both training and testing cohorts (p < 0.001 and p = 0.027, respectively). A significant correlation was observed between the rad-score and E-cad (p < 0.001). PLNM correlated slightly with rad-score and E-cad values (p = 0.01 and p < 0.001, respectively). The ROC curve and calibration curve of the rad-score model performed best in both training and testing cohorts (AUC = 0.915, 0.844, p < 0.001, respectively). CONCLUSIONS: The radiomics of integrating primary tumor and peritumoral areas based on PET-CT showed correlations with PLNM. It was also able to predict E-cad expression in ESCC patients, allowing for evaluation of those patients' prognosis and more individualized medical treatment. KEY POINTS: • By integrating the primary tumor and peritumoral area based on PET-CT, radiomics was feasible. • The rad-score was associated with E-cad expression and PLNM in patients with ESCC. • Radiomics that integrated the primary tumor and peritumoral areas based on PET-CT could predict E-cad expression in patients with ESCC.