Diagnostic value of the Xpert MTB/RIF assay combined with endobronchial ultrasonography with a guide sheath for peripheral nodular pulmonary tuberculosis.

BACKGROUND: The diagnosis of peripheral isolated nodular lesions that are suspected as pulmonary tuberculosis (PTB) is challenging, which are not easily accessible via conventional bronchoscopy. This study evaluated the combined use of Xpert MTB/RIF assay and endobronchial ultrasonography with a guide sheath (EBUS-GS) for detecting MTB infection in peripheral lung bands, for early detection of PTB. METHODS: The clinical data of 232 patients with suspected peripheral nodular PTB who underwent EBUS-GS between June 2020 and October 2023 were retrospectively reviewed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of acid-fast bacilli smear, culture, Xpert MTB/RIF assay, and pathological examination were calculated. To assess diagnostic accuracy, the results of the four methods were directly compared with the final clinical diagnosis. RESULTS: In total, 146 and 86 patients were clinically diagnosed with peripheral nodular PTB and non-PTB, respectively. The sensitivity, specificity, PPV, NPV, and AUC values of combined Xpert MTB/RIF assay and EBUS-GS were 47.26%, 100.0%, 100.0%, 52.76%, and 0.74; those of acid-fast bacilli smear were 8.22%, 97.67%, 85.71%, 38.53%, and 0.53; those of culture were 31.51%, 100.0%, 100.0%, 46.24%, and 0.66; and those of pathological examination were 23.97%, 97.67%, 94.59%, 43.08%, and 0.61, respectively. CONCLUSION: The diagnostic accuracy of the combined Xpert MTB/RIF assay and EBUS-GS was significantly better than that of other conventional tests. Hence, this novel technique can be routinely applied for diagnosing and managing peripheral nodular PTB.

A retrospective study differentiating nontuberculous mycobacterial pulmonary disease from pulmonary tuberculosis on computed tomography using radiomics and machine learning algorithms.

OBJECTIVE: To evaluate the effectiveness of a machine learning based on computed tomography (CT) radiomics to distinguish nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB). METHODS: In this retrospective analysis, medical records of 99 individuals afflicted with NTM-PD and 285 individuals with PTB in Zhejiang Chinese and Western Medicine Integrated Hospital were examined. Random numbers generated by a computer were utilized to stratify the study cohort, with 80% designated as the training cohort and 20% as the validation cohort. A total of 2153 radiomics features were extracted using Python (Pyradiomics package) to analyse the CT characteristics of the large disease areas. The identification of significant factors was conducted through the least absolute shrinkage and selection operator (LASSO) regression. The following four supervised learning classifier models were developed: random forest (RF), support vector machine (SVM), logistic regression (LR), and extreme gradient boosting (XGBoost). For assessment and comparison of the predictive performance among these models, receiver-operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were employed. RESULTS: The Student's t-test, Levene test, and LASSO algorithm collectively selected 23 optimal features. ROC analysis was then conducted, with the respective AUC values of the XGBoost, LR, SVM, and RF models recorded to be 1, 0.9044, 0.8868, and 0.7982 in the training cohort. In the validation cohort, the respective AUC values of the XGBoost, LR, SVM, and RF models were 0.8358, 0.8085, 0.87739, and 0.7759. The DeLong test results noted the lack of remarkable variation across the models. CONCLUSION: The CT radiomics features can help distinguish between NTM-PD and PTB. Among the four classifiers, SVM showed a stable performance in effectively identifying these two diseases.

Antioxidant Enzyme, Transcriptomic, and Metabolomic Changes in Lily (Lilium spp.) Leaves Induced by Aphis gossypii Glover.

Cotton aphids (Aphis gossypii Glover) cause harm by feeding on phloem sap and spreading plant viruses to lily. Understanding the mechanisms by which aphids infest lily plants is crucial for effective aphid management and control. In this study, we investigated the activity of antioxidants, integrated nontargeted metabolomes and transcriptomes of lilies infested by cotton aphids to explore the changes in lily leaves. Overall, the results indicated that the catalase (CAT) activity in the leaves of the lily plants was greater than that in the leaves of the control plants. A comprehensive identification of 604 substances was conducted in the leaves. Furthermore, the differentially abundant metabolite analysis revealed the enrichment of phenylalanine metabolism and α-linolenic acid metabolism. Moreover, 3574 differentially expressed genes (DEGs), whose expression tended to increase, were linked to glutathione metabolism and phenylpropanoid biosynthesis. In addition, the integrated analysis revealed that the defensive response of lily leaves to aphids is manifested through antioxidant reactions, phenylpropane and flavonoid biosynthesis, and α-linolenic acid metabolism. Finally, the key metabolites were CAT, glutathione, coumaric acid, and jasmonic acid, along with the key genes chalcone synthase (CHS), phenylalanine ammonia-lyase (PAL), and 12-oxo-phytodienoic acid reductase (OPR). Accordingly, the findings of this research elucidate the molecular and metabolic reactions of A. gossypii in lily plants, offering valuable insights for developing aphid resistance strategies in lily farming.

Melatonin alleviates brain injury in copper-laden rats: Underlying benefits for Wilson's disease.

Copper serves as an indispensable cofactor for all living organisms, and its excessive accumulation has been associated with a variety of diseases. Wilson's disease (WD) serves as an illustrative example of copper toxicity in humans, frequently presenting with liver and/or neuropsychiatric symptoms. The current therapeutic drugs, penicillamine (PA) and zinc gluconate (ZnG), have constraints, and research on their combination efficacy remains insufficient. It has been reported that melatonin (MLT) plays a vital role in binding to transition metals and exhibits strong antioxidant capacity. To investigate the therapeutic efficacy of MLT and combined treatment, rats were randomly divided into the following seven groups: the control (Con) group, copper-laden model rat (Mod) group, PA-treated group, ZnG-treated group, MLT- treated group, PA-ZnG-treated group, and PA-MLT-treated group. Then potential mechanisms and targets were investigated using a combination of metabolomics and network pharmacology and verified by molecular docking and qPCR. The findings revealed that MLT and the combination significantly improved behavior, pathology and copper levels in copper-laden rats. The results of the metabolomics study showed that profoundly altered metabolites were identified, and alanine, aspartate and glutamate metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis were explored. In addition, molecular docking showed that MLT had high binding affinity with key targets, and qPCR results revealed that MLT could reverse the mRNA expression of targets GOT2 and PKM2. It was concluded that MLT effectively improves brain injury in copper-laden rats, and this effect was linked with the altered features of the metabolite profiles.

Reynoutria multiflora (Thunb.) Moldenke and its ingredient suppress lethal prostate cancer growth by inducing CDC25B-CDK1 mediated cell cycle arrest.

BACKGROUND: Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb, PM) is a medicinal plant that was an element of traditional Chinese medicine (TCM) for centuries as a treatment for a wide range of conditions. Recent studies reported that PM suppressed prostate cancer growth in an AR-dependent manner. However, its role and mechanism in the treatment of advanced prostate cancer remain to be explored. This study aims to explore the anti-tumor role and potential mechanism of PM on prostate cancer. METHODS: Cell viability, colony formation, fluorescence-activated cell sorting (FACS), and wound-healing assays were conducted to evaluate the tumor suppression effect of PM on lethal prostate cancer models in vitro. A xenograft mice model was established to detect the impact of PM on tumor growth and evaluate its biosafety in vivo. Integrative network pharmacology, RNA-seq, and bioinformatics were applied to determine the mechanisms of PM in prostate cancer. Molecular docking, cellular thermal shift assay (CETSA), CRISPR-Cas13, RT-qPCR, and WB were collaboratively employed to identify the potential anti-tumor ingredient derived from PM and its corresponding targets. RESULTS: PM significantly suppressed the growth of prostate cancer and sensitized prostate cancer to AR antagonists. Mechanistically, PM induced G2/M-phase cell-cycle arrest by modulating the phosphorylation of CDK1. Additionally, polygalacic acid derived from PM and its structural analog suppress prostate cancer growth by targeting CDC25B, a master regulator of the cell cycle that governs CDK1 phosphorylation. CONCLUSION: PM and its ingredient polygalacic acid suppress lethal prostate cancer growth by regulating the CDC25B-CDK1 axis to induce cell cycle arrest.

Metabolomic insights into Monascus-fermented rice products: Implications for monacolin K content and nutritional optimization.

This study aims to elucidate the detailed metabolic implications of varying monacolin K levels and sterilization methods on Monascus-fermented rice products (MFRPs), acclaimed for their health benefits and monacolin K content. Advanced metabolite profiling of various MFRP variants was conducted using ultrahigh-performance liquid chromatography coupled with tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS). Statistical analysis encompassed t-tests, ANOVA, and multivariate techniques including PCA, PLS-DA, and OPLS-DA. Notable variations in metabolites were observed across MFRPs with differing monacolin K levels, particularly in variants such as MR1-S, MR1.5-S, MR2-S, and MR3-S. Among the 524 identified metabolites, significant shifts were noted in organic acids, derivatives, lipids, nucleosides, and organic oxygen compounds. The study also uncovered distinct metabolic changes resulting from different sterilization methods and the use of highland barley as a fermentation substitute for rice. Pathway analysis shed light on affected metabolic pathways, including those involved in longevity regulation, cGMP-PKG signaling, and the biosynthesis of unsaturated fatty acids. The research provides critical insights into the complex metabolic networks of MFRPs, underscoring the impact of fermentation substrates and conditions on monacolin K levels and their health implications. This study not only guides the nutritional optimization of MFRPs but also emphasizes the strategic importance of substrate choice and sterilization techniques in enhancing the nutritional and medicinal value of these functional foods.

Global, regional, and national burden of cancers attributable to occupational risks from 1990 to 2019.

BACKGROUND: Based on data from the Global Burden of Disease study, the burden of cancer attributable to occupational risks between 1990 and 2019 was explored. METHODS: The estimated burden in different regions was compared in terms of the age-standardized death rates (ASDRs), age-standardized disability-adjusted life years (DALYs) rates, and corresponding estimated annual percentage changes (EAPCs). The comparative risk assessment framework was used to estimate the risk of death and DALYs attributable to occupational risk factors. RESULTS: Globally from 1990 to 2019, ASDRs decreased (EAPC = -0.69; 95% CI: -0.76 to -0.61), and age-standardized DALY rates decreased (EAPC = -0.99; 95% CI: -1.05 to -0.94). In terms of the global age distribution of cancer attributable to occupational risk factors, the death rate and DALY rates increased with age. In addition, from 1990 to 2019, the number of deaths, DALYs, ASDRs, and age-standardized DALY rates in men were higher than those in women, and the cancer burden grew fastest in Georgia (EAPC = 5.04), Croatia (EAPC = 4.01), and Honduras (EAPC = 3.54). Moreover, as the sociodemographic index (SDI) value of a country or region increased, its burden of cancer attributable to occupational risk factors rapidly increased. CONCLUSIONS: The global cancer burden attributable to occupational risk factors declined from 1990 to 2019, was higher in men than in women, and was concentrated in middle-aged and older adults. The baseline cancer burdens of regions or countries increased as their SDI values increased and were especially high in high-SDI regions or countries.

Associations of prenatal exposure to PM2.5 and its components with offsprings' neurodevelopmental and behavioral problems: A prospective cohort study from China.

Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14-1.18 per µg/m3 in the first trimester; 1.15, 1.12-1.17 in the second trimester; 1.06, 1.04-1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Material Composition Characteristics of Aspergillus cristatus under High Salt Stress through LC-MS Metabolomics.

Aspergillus cristatus is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis was performed to analyze the distribution and composition of A. cristatus under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC-MS metabolomics analysis revealed significant differences between three A. cristatus mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of A. cristatus mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that A. cristatus adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition.

Astragaloside IV inhibits colorectal cancer metastasis by reducing extracellular vesicles release and suppressing M2-type TAMs activation.

Ethnopharmacological relevance: Tumour-derived extracellular vesicles (TEVs) have been confirmed to facilitate colorectal cancer (CRC) metastasis by remodelling the tumour microenvironment (TME). Drugs targeted TEVs is considered as a promising therapeutic strategy for cancer treatment. Traditional Chinese medicine (TCM) plays a vital role in improving the prognosis of CRC patients and eventually CRC patients with distant metastasis. Although the anti-tumour effects of active compounds from TCM prescriptions are observed widely, the molecular mechanisms remain unknown. Aim of the study: This study aims to investigate the effects of active compounds in our library of TCM on preventing CRC metastasis, and also explore the potential mechanisms from the perspective of TEVs. Materials and methods: The effects of active compounds on the proliferation of CRC cells were determined by CCK-8 assay. TEVs were extracted from MC38 cells by ultracentrifugation and characterized by electron microscopy, Nanosight NS300 and western blotting. The TEV particles were quantified by Nanosight NS300. The potential mechanism by which astragaloside IV (ASIV) reduced TEV secretion was determined by western blotting. RAW264.7 cells were cocultured with the conditioned medium (CM) of MC38 cells treated with or without ASIV, and the activation of tumour-associated macrophages (TAMs) was assessed by immunofluorescence and quantitative polymerase chain reaction (qPCR). The migration of CRC cells was measured by wound healing and Transwell assay. A spleen-to-liver metastasis model of colorectal cancer was used to confirm the efficiency of ASIV in vivo. Liver metastatic tumours of the mice were used for liver weight measures and H&E staining. Immunofluorescence was applied to observe the infiltration of TAMs, the expression of neutral sphingomyelinase 2 (nSMase2) and Rab27a. Results: By screening our TCM monomer library, we found that ASIV, which is mainly extracted from Radix Astragali, reduced the release of TEVs from CRC cells in a time- and concentration-dependent manner. Mechanistically, ASIV inhibited the production and secretion of TEVs by downregulating nSMase2 and Rab27a expression in CRC cells. CM from ASIV-treated CRC cells reshaped the polarization of TAMs by decreasing M2-type polarization, increasing M1-type polarization. Consequently, the repolarization of M2-type to M1-type macrophages led to reduced invasion and migration of CRC cells. Moreover, we confirmed that ASIV inhibited the liver metastasis of CRC, reduced M2-type macrophage infiltration and decreased the expression of nSMase2 and Rab27a in liver metastases. Conclusions: ASIV inhibited CRC metastasis by reducing EVs release and suppressing M2-type TAMs activation. All these findings reveal a new insight into the mechanisms of ASIV in preventing CRC progression and provide a promising approach for anti-tumour therapy.

Using cerebrospinal fluid nanopore sequencing assay to diagnose tuberculous meningitis: a retrospective cohort study in China.

OBJECTIVE: This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF). DESIGN: Single-centre retrospective study. SETTING: The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital. PARTICIPANTS: We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023. METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM. RESULTS: Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively. CONCLUSION: The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.

Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression.

Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.

The Brachypodium distachyon DREB transcription factor BdDREB-39 confers oxidative stress tolerance in transgenic tobacco.

Key message BdDREB-39 is a DREB/CBF transcription factor, localized in the nucleus with transactivation activity, and BdDREB-39-overexpressing transgenic yeasts and tobacco enhanced the tolerance to oxidative stress.Abstract The DREB/CBF transcription factors are generally recognized to play an important factor in plant growth, development and response to various abiotic stresses. However, the mechanism of DREB/CBFs in oxidative stress response is largely unknown. This study isolated a DREB/CBF gene BdDREB-39 from Brachypodium distachyon (B. distachyon). Multiple sequence alignment and phylogenetic analysis showed that BdDREB-39 was closely related to the DREB proteins of oats, barley, wheat and rye and therefore its study can provide a reference for the excavation and genetic improvement of BdDREB-39 or its homologs in its closely related species. The transcript levels of BdDREB-39 were significantly up-regulated under H2O2 stress. BdDREB-39 was localised in the nucleus and functioned as a transcriptional activator. Overexpression of BdDREB-39 enhanced H2O2 tolerance in yeast. Transgenic tobaccos with BdDREB-39 had higher germination rates, longer root, better growth status, lesser reactive oxygen species (ROS) and malondialdehyde (MDA), and higher superoxide dismutase (SOD) and peroxidase (POD) activities than wild type (WT). The expression levels of ROS-related and stress-related genes were improved by BdDREB-39. In summary, these results revealed that BdDREB-39 can improve the viability of tobacco by regulating the expression of ROS and stress-related genes, allowing transgenic tobacco to accumulate lower levels of ROS and reducing the damage caused by ROS to cells. The BdDREB-39 gene has the potential for developing plant varieties tolerant to stress.

Population dynamics and seasonal migration patterns of Spodoptera exigua in northern China based on 11 years of monitoring data.

Background: The beet armyworm, Spodoptera exigua (Hübner), is an important agricultural pest worldwide that has caused serious economic losses in the main crop-producing areas of China. To effectively monitor and control this pest, it is crucial to investigate its population dynamics and seasonal migration patterns in northern China. Methods: In this study, we monitored the population dynamics of S. exigua using sex pheromone traps in Shenyang, Liaoning Province from 2012 to 2022, combining these data with amigration trajectory simulation approach and synoptic weather analysis. Results: There were significant interannual and seasonal variations in the capture number of S. exigua, and the total number of S. exigua exceeded 2,000 individuals in 2018 and 2020. The highest and lowest numbers of S. exigua were trapped in September and May, accounting for 34.65% ± 6.81% and 0.11% ± 0.04% of the annual totals, respectively. The average occurrence period was 140.9 ± 9.34 days during 2012-2022. In addition, the biomass of S. exigua also increased significantly during these years. The simulated seasonal migration trajectories also revealed varying source regions in different months, primarily originated from Northeast China and East China. These unique insights into the migration patterns of S. exigua will contribute to a deeper understanding of its occurrence in northern China and provide a theoretical basis for regional monitoring, early warning, and the development of effective management strategies for long-range migratory pests.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

Changes in cargoes of platelet derived extracellular vesicles heterogeneous subpopulations induced by PM0.1--Undisclosed cardiovascular injury communication mechanism.

Epidemiological evidence has indicated a closely link between PM0.1 exposure and the incidence rate of cardiovascular diseases. This study explores the underlying communication roles of platelet-derived extracellular vesicles (PEVs) heterogeneous subpopulations in cardiovascular injury. PEVs and PMEVs which were extracted from platelet-rich plasma (PRP) un-exposure or exposure to PM0.1 by TIM4 affinity beads. By optimizing separation conditions, replacing pipelines, and resetting injection procedures, Asymmetric flow field-flow fractionation (AF4) was employed to separate, purify, characterize, and enrich PEVs and PMEVs heterogeneous subpopulations (small PEVs, PEVs-S/PMEVs-S: <100 nm; medium PEVs, PEVs-M/PMEVs-M: 100-200 nm; and large PEVs, PEVs-L/PMEVs-L: >200 nm). The results showed that the cargoes of PMEVs heterogeneous subpopulations which were released by PRP stimulated by PM0.1 were changed obviously. Moreover, compared with PEVs, PMEVs can lead to a decrease in the survival rate of Human Umbilical Vein Endothelial Cells (HUVECs). In PMEVs-S subpopulations, the alterations of lipids associated with membrane fusion and cell signaling transport (such as PC, Cer), as well as miRNAs related to inflammation, angiogenesis, and migration (miR-223, miR-22, miR-126, and miR-150), are similar to those in PMEVs-M subpopulations but distinct from PMEVs-L subpopulations. This study revealed the diverse communication mechanisms underlying PM0.1-induced cardiovascular injury, thereby offering potential avenues for the development of new biomarkers and therapeutic targets.

Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Associations of prenatal exposure to per- and polyfluoroalkyl substances and fetal sex hormones in the Guangxi Zhuang Birth Cohort Study: Greater effect of long-chain PFAS.

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.

Image-based vegetation analysis of desertified area by using a combination of ImageJ and Photoshop software.

Fractional vegetation cover (FVC) is a crucial indicator to estimate degradation and desertification for grasslands. However, traditional small-scale FVC analysis methods, such as visual estimation and point-sampling, are cumbersome and imprecise. Innovative methods like image-based FVC analysis methods, while accurate, face challenges such as complex analytical procedures and the necessary training for operations. Therefore, in this study, a combined application of ImageJ and Photoshop was employed to achieve a more effective analysis of FVC values in desertification areas. Our results showed that the FVC results obtained by combination of Photoshop and ImageJ were dependable and precise (R2 > 0.98), demonstrating equivalency to results obtained through either visual estimation or Photoshop-based methods. Furthermore, even in the face of background interference and varied shooting angles, the combination of ImageJ and Photoshop software was still able to maintain a low error rate when analyzing FVC values (average error rate = - 2.6%). In conclusion, the imaged-based combined FVC analysis method employed in our research was an effective, precise, and efficient technique for analyzing small-scale FVC, promising substantial improvement over conventional methods.

TET3-mediated novel regulatory mechanism affecting trophoblast invasion and migration: Implications for preeclampsia development.

INTRODUCTION: Aberrant expression of genes has been demonstrated to be related to the abnormal function of trophoblasts and lead to the occurrence and progression of Preeclampsia (PE). However, the underlying mechanism of PE has not been elucidated. METHODS: We performed PCR analysis to investigate TET3 expression in PE placental tissues. Cell assays were performed in HTR-8/SVneo and JAR. Cell invasion and migration events were investigated by transwell assays in vitro. ChIP-PCR and Targeted bisulfite sequencing were conducted to detect the demethylation of related CpG sites in the KLF13 promoter after inhibition of TET3. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR-544 binds to TET3/KLF13 mRNA. RESULTS: In this study, we identified genes associated with human extravillous trophoblasts by conducting sc-seq analysis from the GEO. Then, we measured the expression of TET3 in a larger clinical sample. The results showed that TET3, a DNA demethylase, was found to be expressed at much higher levels in the preeclamptic placenta compared to the control. Then, the inhibition of TET3 significantly promoted trophoblast cell migration and invasion. Conversely, TET3 overexpression suppressed cell migration and invasion in vitro. Further RNA sequencing and mechanism analysis indicated that the inhibition of TET3 suppressed the activation of KLF13 by reducing the demethylation of related CpG sites in the KLF13 promoter, thereby transcriptionally inactivating KLF13 expression. Moreover, luciferase reporter assay indicate that TET3 and KLF13 were direct targets of miR-544. DISCUSSION: This study uncovers a TET3-mediated regulatory mechanism in PE progression and suggests that targeting the placental miR-544-TET3-KLF13-axis might provide new diagnostic and therapeutic strategies for PE.