Combined effects of micron-sized polyvinyl chloride particles and copper on seed germination of perilla.

Microplastics (MPs) and copper (Cu) pollution coexist widely in cultivation environment. In this paper, polyvinyl chloride (PVC) were used to simulate the MPs exposure environment, and the combined effects of MPs + Cu on the germination of perilla seeds were analyzed. The results showed that low concentrations of Cu promoted seed germination, while medium to high concentrations exhibited inhibition and deteriorated the morphology of germinated seeds. The germination potential, germination index and vitality index of 8 mg • L-1 Cu treatment group with were 23.08%, 76.32% and 65.65%, respectively, of the control group. The addition of low concentration PVC increased the above indicators by 1.27, 1.15, and 1.35 times, respectively, while high concentration addition led to a decrease of 65.38%, 82.5%, and 66.44%, respectively. The addition of low concentration PVC reduced the amount of PVC attached to radicle. There was no significant change in germination rate. PVC treatment alone had no significant effect on germination. MPs + Cu inhibited seed germination, which was mainly reflected in the deterioration of seed morphology. Cu significantly enhanced antioxidant enzyme activity, increased reactive oxygen species (ROS) and MDA content. The addition of low concentration PVC enhanced SOD activity, reduced MDA and H2O2 content. The SOD activity of the Cu2+8 + PVC10 group was 4.05 and 1.35 times higher than that of the control group and Cu treatment group at their peak, respectively. At this time, the CAT activity of the Cu2+8 + PVC5000 group increased by 2.66 and 1.42 times, and the H2O2 content was 2.02 times higher than the control. Most of the above indicators reached their peak at 24 h. The activity of α-amylase was inhibited by different treatments, but ß-amylase activity, starch and soluble sugar content did not change regularly. The research results can provide new ideas for evaluating the impact of MPs + Cu combined pollution on perilla and its potential ecological risk.

Enhancing barley yield potential and germination rate: gene editing of HvGA20ox2 and discovery of novel allele sdw1.ZU9.

Several dwarf and semi-dwarf genes have been identified in barley. However, only a limited number have been effectively utilized in breeding programs to cultivate lodging resistant varieties. This is due to the common association of dwarf and semi-dwarf traits with negative effects on malt quality. In this study, we employed gene editing to generate three new haplotypes of sdw1/denso candidate gene gibberellin (GA) 20-oxidase2 (GA20ox2). These haplotypes induced a dwarfing phenotype and enhancing yield potential, and promoting seed dormancy, thereby reducing pre-harvest sprouting. Moreover, ß-amylase activity in the grains of the mutant lines was significantly increased, which is beneficial for malt quality. The haplotype analysis revealed significant genetic divergence of this gene during barley domestication and selection. A novel allele (sdw1.ZU9), containing a 96-bp fragment in the promoter region of HvGA20ox2, was discovered and primarily observed in East Asian and Russian barley varieties. The 96-bp fragment was associated with lower gene expression, leading to lower plant height but higher germination rate. In conclusion, HvGA20ox2 can be potentially used to develop semi-dwarf barley cultivars with high yield and improved malt quality.

Staphylococcus aureus promotes its intracellular survival by inhibiting Rab11-Rab11FIP4-mediated vesicle trafficking.

Mastitis in dairy cows is mainly caused by bacteria, in which Staphylococcus aureus appears frequently. Epithelial cells, as a major physical barrier of mammary gland, play an important role in preventing mastitis in dairy cows. Our previous study reported that Rab11fip4 (an effector of Rab11) was significantly changed in response to stimulation by S. aureus. So, in this study, the role of Rab11A in phagocytosis of bovine mammary epithelial cells (MAC-T) against S. aureus was evaluated. First, changes of Rab11A and Rab11fip4 were analyzed in response to S. aureus by immunofluorescence and western blotting. Subsequently, the effects of Rab11A and Rab11fip4 on proliferation of S. aureus, as well as formation and function of late endosomes (LEs) and lysosomes (LYSs) were investigated. The results showed that, after infection, Rab11A and Rab11fip4 were recruited to phagosomes containing S. aureus. Rab11A promoted bacterial clearance and rescues the destruction of LEs and LYSs by S. aureus, whereas Rab11fip4 did the opposite. These findings provide new insights into phagocytosis and control of S. aureus in host cells, thus lay the foundation to elucidate the pathogenesis of S. aureus in bovine mastitis.

Combined effect of freshwater salinization and harmful algae on the benthic invertebrate Chironomus pallidivittatus.

Global climate change as well as human activities have been reported to increase the frequency and severity of both salinization and harmful algal blooms (HABs) in many freshwater systems, but their co-effect on benthic invertebrates has rarely been studied. This study simultaneously examined the joint toxicity of salinity and different cyanobacterial diets on the behavior, development, select biomarkers, and partial life cycle of Chironomus pallidivittatus (Diptera). High concentrations of salts (e.g., 1 g/L Ca2+ and Mg2+) and toxic Microcystis had synergistic toxicity, inhibiting development, burrowing ability and causing high mortality of C. pallidivittatus, especially for the Mg2+ treatment, which caused around 90% death. Low Ca2+ concentration (e.g., 0.01 g/L) promoted larval burrowing ability and inhibited toxin accumulation, which increased the tolerance of Chironomus to toxic Microcystis. However, low Mg2+ concentration (e.g., 0.01 g/L) was shown to inhibit the behavior, development and increase algal toxicity to Chironomus. Toxic Microcystis resulted in microcystin (MC) accumulation, inhibited the burrowing ability of larvae, and increased the proportion of male adults (>50%). The combined toxicity level from low to high was verified by the weight of evidence and the grey TOPSIS model, which integrated five lines of evidence to increase the risk assessment accuracy and efficiency. This is the first study that provided insights into ecological risk arising from the joint effect of salinity and harmful algae on benthic organisms. We suggest that freshwater salinization and HABs should be considered together when assessing ecological threats that arise from external stress.

Image Understands Point Cloud: Weakly Supervised 3D Semantic Segmentation via Association Learning.

Weakly supervised point cloud semantic segmentation methods that require 1% or fewer labels with the aim of realizing almost the same performance as fully supervised approaches have recently attracted extensive research attention. A typical solution in this framework is to use self-training or pseudo-labeling to mine the supervision from the point cloud itself while ignoring the critical information from images. In fact, cameras widely exist in LiDAR scenarios, and this complementary information seems to be highly important for 3D applications. In this paper, we propose a novel cross-modality weakly supervised method for 3D segmentation that incorporates complementary information from unlabeled images. We design a dual-branch network equipped with an active labeling strategy to maximize the power of tiny parts of labels and to directly realize 2D-to-3D knowledge transfer. Afterward, we establish a cross-modal self-training framework, which iterates between parameter updating and pseudolabel estimation. In the training phase, we propose cross-modal association learning to mine complementary supervision from images by reinforcing the cycle consistency between 3D points and 2D superpixels. In the pseudolabel estimation phase, a pseudolabel self-rectification mechanism is derived to filter noisy labels, thus providing more accurate labels for the networks to be fully trained. The extensive experimental results demonstrate that our method even outperforms the state-of-the-art fully supervised competitors with less than 1% actively selected annotations.

Selecting Monoclonal Cell Lineages from Somatic Reprogramming Using Robotic-Based Spatial-Restricting Structured Flow.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

The mediating role of atrial fibrillation in causal associations between risk factors and stroke: a Mendelian randomization study.

OBJECTIVES: Atrial fibrillation (AF) contributes to stroke development and progression. We aimed to quantify the mediating role of AF in the causal associations between a wide range of risk factors and stroke via a Mendelian randomization (MR) framework. METHODS: We assessed the associations of 108 traits with stroke and its subtypes in a 2-sample univariable MR approach, then conducted a bidirectional MR analysis between these 108 traits and AF to evaluate the presence and direction of their causal associations. Finally, to further investigate the extent to which AF mediated the effects of eligible traits on stroke, we applied multivariable and 2-step MR techniques in a mediation analysis where outcomes were restricted to stroke types causally affected by AF (any stroke [AS], any ischemic stroke [AIS], and cardioembolic stroke [CES]). RESULTS: Among 108 traits, 42 were putatively causal for at least 1 stroke type; of these 42 traits, 20 that had no bidirectional relationship with AF were retained. Finally, 33 associations of 15 eligible traits were examined in the mediation analysis. The mediation analyses for AS, AIS, and CES each included 11 eligible traits. After AF adjustment, the direct effects of all traits on CES were attenuated to null (all p>0.05), while the associations with AS and AIS persisted for most traits (AF-mediated proportion: from 6.6% [95% confidence interval, 2.7 to 0.6] to 52.0% [95% confidence interval, 39.8 to 64.3]). CONCLUSIONS: The causal associations between all eligible traits and CES were largely mediated through AF, while most traits affected AS and AIS independently of AF.

Adiposity and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study

BACKGROUND AND OBJECTIVES: To investigate the causal relationships of abdominal adiposity (waist-to-hip ratio [WHR]) and overall adiposity (body mass index [BMI]) with functional outcome after ischemic stroke using Mendelian randomization. METHODS: Genetic instruments for WHR and BMI were obtained from the largest available genome-wide association studies meta-analysis of the Genetic Investigation of ANthropometric Traits consortium and the UK Biobank (N max = 806,834). Functional outcome after ischemic stroke was assessed using the modified Rankin Scale (mRS) score at 3-month after stroke onset, with mRS >2 (mRS 3-6) defined as an unfavorable functional outcome. Corresponding genetic estimates for an unfavorable functional outcome were extracted from the Genetics of Ischemic Stroke Functional Outcome network (N = 6,021). We applied a random-effects inverse variance weighted method as our main analysis. RESULTS: Genetically predicted higher WHR (per 0.09 ratio units) was associated with unfavorable functional outcome after ischemic stroke (mRS 3-6, OR = 1.48; 95% CI = 1.03-2.13; p = 0.033). The results remained directionally consistent in sensitivity analyses. Conversely, genetically predicted BMI (per 4.8 kg/m2) was not associated with unfavorable functional outcome after ischemic stroke (OR = 1.01; 95% CI = 0.75-1.36; p = 0.937). DISCUSSION: This study provides genetic evidence supporting the hypothesis that abdominal adiposity has a detrimental effect on functional recovery after ischemic stroke.

Serum uric acid and prognosis of ischemic stroke: Cohort study, meta-analysis and Mendelian randomization study.

INTRODUCTION: The role of serum uric acid (UA) levels in the functional recovery of ischemic stroke remains uncertain. To evaluate whether UA could predict clinical outcomes in patients with ischemic stroke. PATIENTS AND METHODS: A three-stage study design was employed, combining a large-scale prospective cohort study, a meta-analysis and a Mendelian randomization (MR) analysis. Firstly, we conducted a cohort study using data from the Nanjing Stroke Registry Program (NSRP) to assess the association between UA levels and 3-month functional outcomes in ischemic stroke patients. Secondly, the meta-analysis was conducted to integrate currently available cohort evidence. Lastly, MR analysis was utilized to explore whether genetically determined UA had a causal link to the functional outcomes of ischemic stroke using summary data from the CKDGen and GISCOME datasets. RESULTS: In the first stage, the cohort study included 5631 patients and found no significant association between UA levels and functional outcomes at 3 months after ischemic stroke. In the second stage, the meta-analysis, including 10 studies with 14,657 patients, also showed no significant association between UA levels and stroke prognosis. Finally, in the third stage, MR analysis using data from 6165 patients in the GISCOME study revealed no evidence of a causal relationship between genetically determined UA and stroke functional outcomes. DISCUSSION AND CONCLUSION: Our comprehensive triangulation approach found no significant association between UA levels and functional outcomes at 3 months after ischemic stroke.

Variational Distillation for Multi-View Learning.

Information Bottleneck (IB) provides an information-theoretic principle for multi-view learning by revealing the various components contained in each viewpoint. This highlights the necessity to capture their distinct roles to achieve view-invariance and predictive representations but remains under-explored due to the technical intractability of modeling and organizing innumerable mutual information (MI) terms. Recent studies show that sufficiency and consistency play such key roles in multi-view representation learning, and could be preserved via a variational distillation framework. But when it generalizes to arbitrary viewpoints, such strategy fails as the mutual information terms of consistency become complicated. This paper presents Multi-View Variational Distillation (MV 2 D), tackling the above limitations for generalized multi-view learning. Uniquely, MV 2 D can recognize useful consistent information and prioritize diverse components by their generalization ability. This guides an analytical and scalable solution to achieving both sufficiency and consistency. Additionally, by rigorously reformulating the IB objective, MV 2 D tackles the difficulties in MI optimization and fully realizes the theoretical advantages of the information bottleneck principle. We extensively evaluate our model on diverse tasks to verify its effectiveness, where the considerable gains provide key insights into achieving generalized multi-view representations under a rigorous information-theoretic principle.

MiR-150-5p Alleviates Renal Tubular Epithelial Cell Fibrosis by Activating Autophagy via ß-catenin Signaling.

OBJECTIVE: To verify whether miR-150-5p modulates the development of renal fibrosis and its mechanism. METHODS: Transforming growth factor (TGF)-ß1 was implemented on HK-2 cells to construct a renal fibrosis in vitro model. Inhibition of autophagy was performed on HK-2 cells by treating with 3-methyladenine (3-MA, an inhibitor of autophagy). HK-2 cells experienced transfection by miR-150-5p mimics/inhibitor and pcDNA-ß-catenin plasmids, and the negative controls. Dual luciferase reporter gene assay was applied to validate the relationship between miR-150-5p and ß-catenin. Cell apoptosis exploration was implemented by flow cytometry assay. The level detection of CoII, α-SMA, miR-150-5p and ß-catenin was executed by real-time quantitative reverse transcription-polymerase chain reaction. The expression of CoII, α-SMA, LC3I, LC3II, Bax, Cleaved Caspase 3, Beclin 1, Bcl-2 and ß-catenin proteins was monitored by western blot. RESULTS: Autophagy was inhibited in TGF-ß1-induced HK-2 cells. MiR-150-5p alleviated fibrosis, enhanced autophagy, and inhibited apoptosis in TGF-ß1-induced HK-2 cells. ß-catenin was a target of miR-150-5p. Autophagy inhibition or ß-catenin partially counteracted miR-150-5p effect on TGF-ß1-induced fibrosis in HK-2 cells. CONCLUSIONS: MiR-150-5p alleviates renal tubular epithelial cell fibrosis by activating autophagy via ß-catenin signaling.

Positive-Negative Receptive Field Reasoning for Omni-Supervised 3D Segmentation.

Hidden features in the neural networks usually fail to learn informative representation for 3D segmentation as supervisions are only given on output prediction, while this can be solved by omni-scale supervision on intermediate layers. In this paper, we bring the first omni-scale supervision method to 3D segmentation via the proposed gradual Receptive Field Component Reasoning (RFCR), where target Receptive Field Component Codes (RFCCs) is designed to record categories within receptive fields for hidden units in the encoder. Then, target RFCCs will supervise the decoder to gradually infer the RFCCs in a coarse-to-fine categories reasoning manner, and finally obtain the semantic labels. To purchase more supervisions, we also propose an RFCR-NL model with complementary negative codes (i.e., Negative RFCCs, NRFCCs) with negative learning. Because many hidden features are inactive with tiny magnitudes and make minor contributions to RFCC prediction, we propose Feature Densification with a centrifugal potential to obtain more unambiguous features, and it is in effect equivalent to entropy regularization over features. More active features can unleash the potential of omni-supervision method. We embed our method into three prevailing backbones, which are significantly improved in all three datasets on both fully and weakly supervised segmentation tasks and achieve competitive performances.

Comparison of miRNA transcriptome of exosomes in three categories of somatic cells with derived iPSCs.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) through epigenetic manipulation. While the essential role of miRNA in reprogramming and maintaining pluripotency is well studied, little is known about the functions of miRNA from exosomes in this context. To fill this research gap,we comprehensively obtained the 17 sets of cellular mRNA transcriptomic data with 3.93 × 1010 bp raw reads and 18 sets of exosomal miRNA transcriptomic data with 2.83 × 107 bp raw reads from three categories of human somatic cells: peripheral blood mononuclear cells (PBMCs), skin fibroblasts(SFs) and urine cells (UCs), along with their derived iPSCs. Additionally, differentially expressed molecules of each category were identified and used to perform gene set enrichment analysis. Our study provides sets of comparative transcriptomic data of cellular mRNA and exosomal miRNA from three categories of human tissue with three individual biological controls in studies of iPSCs generation, which will contribute to a better understanding of donor cell variation in functional epigenetic regulation and differentiation bias in iPSCs.

Risk stratification algorithm for clinical outcomes in anemic patients undergoing percutaneous coronary intervention.

BACKGROUND: To explore the crosstalk between baseline or visit hemoglobin and major adverse cardiovascular and cerebral events (MACCE) in percutaneous coronary intervention (PCI) patients and to construct risk stratification models to predict MACCE amongst these patients. MATERIALS AND METHODS: We conducted a retrospective cohort in patients undergoing PCI procedures at Beijing Friendship Hospital between January 2013 and December 2020. Multivariate Cox proportional hazards models were employed for data analyses. The composite MACCE was the primary endpoint and we used machine learning algorithms to evaluate risk factors associated with MACCE. Model performance was measured using Brier scores and receiver-operating characteristic curves. The association between risk factors and MACCE probability was examined using partial dependency plots. RESULTS: 8,298 PCI-treated patients were enrolled in the study. 1,919 of these patients had anemia. During a four-year median follow-up period, 1,636 patients (19.71%) had MACCE. The visit hemoglobin and hemoglobin change was associated with higher risk of MACCE respectively (visit hemoglobin: hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.98-0.99; p < 0.001; hemoglobin change: HR: 0.99; 95%CI: 0.98-0.99; p < 0.001). Gradient Boosting (GB) was the BPM, with a mean C-statistic value of 0.78 (95% CI: 0.76-0.80) for predicting MACCE (Brier score: 0.26). The best indicator for MACCE was a low estimated glomerular filtration rate [eGFR] (71 mL/min/1.73m2) at admission, followed by a high serum HbA1c (6.6%) level. A simple risk tree successfully classified patients (17-40.5%) with increased risks of MACCE. The high- vs. low-risk HR for MACCE was 2.04 (95% CI: 1.48-2.82). CONCLUSIONS: Visit hemoglobin and long-term hemoglobin changes were more predictive of MACCE risk than baseline hemoglobin levels. Our findings indicated that increasing hemoglobin levels might improve the long-term prognosis of anemia patients. We established a new risk stratification model for MACCE, which may more efficiently prioritize targeted screening for at-risk anemic patients undergoing PCI.

Visit hemoglobin and long-term hemoglobin changes predicted the risk of MACCE better than baseline hemoglobin.Patients with anemia will benefit from increasing hemoglobin levels.A new risk stratification model for MACCE was established to identify at-risk anemic patients undergoing PCI.

Developing a questionnaire to evaluate the health information literacy in China.

Introduction: Health information literacy is critical for individuals to obtain, understand, screen, and apply health information. However, there is currently no specific tool available to evaluate all four dimensions of health information literacy in China. Public health emergencies can present an opportunity to evaluate and monitor the health information literacy level of residents. Therefore, this study aimed to develop a questionnaire to evaluate the level of health information literacy and to measure the reliability and validity. Methods: The development process of the questionnaire consisted of the determination of questionnaire items, expert consultation, and validation. Based on the National Residents Health Literacy Monitoring Questionnaire (2020) and the 2019 Informed Health Choices key concepts, the researchers drafted the questionnaire, including all four dimensions of health information literacy. Experts in relevant fields were invited to evaluate the draft questionnaire, and revisions were made accordingly. Finally, the reliability and validity of the finalized version were examined in Gansu Province, China. Results: The research team preliminarily formulated 14 items encompassing the four dimensions of health information literacy. After consulting with 28 experts, modifications were made. A convenience sample of 185 Chinese residents was invited to participate. Cronbach's alpha coefficient was 0.715 and McDonald's omega was 0.739 for internal consistency, and the test-retest intra-class correlation coefficient after 4 weeks was 0.906, indicating that the questionnaire content and measurement structure was relatively stable. Conclusion: This questionnaire is the first evidence-based assessment tool developed for monitoring health information literacy in China, and it has shown good reliability and validity. It can help to monitor the health information literacy levels of Chinese residents, promote evidence-based decision-making, and guide interventions to improve health information literacy.

Coexistence of Magnon-Induced and Rashba-Induced Unidirectional Magnetoresistance in Antiferromagnets.

Unidirectional magnetoresistance (UMR) has been intensively studied in ferromagnetic systems, which is mainly induced by spin-dependent and spin-flip electron scattering. Yet, UMR in antiferromagnetic (AFM) systems has not been fully understood to date. In this work, we reported UMR in a YFeO3/Pt heterostructure where YFeO3 is a typical AFM insulator. Magnetic-field dependence and temperature dependence of transport measurements indicate that magnon dynamics and interfacial Rashba splitting are two individual origins for AFM UMR, which is consistent with the UMR theory in ferromagnetic systems. We further established a comprehensive theoretical model that incorporates micromagnetic simulation, density functional theory calculation, and the tight-binding model, which explain the observed AFM UMR phenomenon well. Our work sheds light on the intrinsic transport property of the AFM system and may facilitate the development of AFM spintronic devices.

The Impact of Genetically Proxied AMPK Activation, the Target of Metformin, on Functional Outcome Following Ischemic Stroke.

BACKGROUND AND PURPOSE: We performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of genetically proxied AMP-activated protein kinase (AMPK) activation, which is the target of metformin, on functional outcome following ischemic stroke onset. METHODS: A total of 44 AMPK-related variants associated with HbA1c (%) were used as instruments for AMPK activation. The primary outcome was the modified Rankin Scale (mRS) score at 3 months following the onset of ischemic stroke, evaluated as a dichotomous variable (3-6 vs. 0-2) and subsequently as an ordinal variable. Summary-level data for the 3-month mRS were obtained from the Genetics of Ischemic Stroke Functional Outcome network, including 6,165 patients with ischemic stroke. The inverse-variance weighted method was used to obtain causal estimates. The alternative MR methods were used for sensitivity analysis. RESULTS: Genetically predicted AMPK activation was significantly associated with lower odds of poor functional outcome (mRS 3-6 vs. 0-2, odds ratio [OR]: 0.06, 95% confidence interval [CI]: 0.01-0.49, P=0.009). This association was maintained when 3-month mRS was analyzed as an ordinal variable. Similar results were observed in the sensitivity analyses, and there was no evidence of pleiotropy. CONCLUSION: This MR study provided evidence that AMPK activation by metformin may exert beneficial effects on functional outcome following ischemic stroke.

Staphylococcus aureus extracellular vesicles induce apoptosis and restrain mitophagy-mediated degradation of damaged mitochondria.

Extracellular vesicles (EVs) are nano-sized bilayer EVs with various components. EV secretion in pathogenic Gram-positive bacteria is a universal feature that can cause disease and damage the targeted host. In this study, we isolated and purified Staphylococcus aureus (S. aureus) EVs, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyzed Ev's protein composition. After that, the pathway of EVs internalized into MAC-T cells was evaluated. Moreover, the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor κB (NF-κB) pathway was measured by Western blot. Meanwhile, Western blot and confocal microscopy detected mitochondrial damage, apoptosis, and Parkin-mediated mitophagy. Results showed that purified S. aureus EVs exhibited a typical cup-shaped structure and internalized into MAC-T cells by lipid raft-mediated endocytic pathway. S. aureus EVs caused mitochondrial damage and apoptosis in MAC-T cells. However, degradation of the damaged mitochondria was impeded due to the Parkin-mediated mitophagy pathway being restrained by the disruption of the acidic environment of lysosomes by S. aureus EVs. Hence, our study reveals the role of S. aureus EVs in immune stimulation, disruption of mitochondria, and lysosomal acidic environment in bovine mammary epithelial cells. These findings help us understand the role of EVs in the pathogenic mechanism of S. aureus.

Physiological analysis and transcriptome profiling reveals the impact of microplastic on melon (Cucumis melo L.) seed germination and seedling growth.

The wide application of agricultural plastics leads to microplastic (MP) accumulation in the soil and inevitably result in MP pollution. Melon is an economically important horticultural crop that is widely cultivated with plastic film mulching. However, the impact of MP pollution on plant growth remains largely unclear. Here we reported the morphological, physiological, biochemical responses and transcriptome re-programing of melon responses to MP on seed germination and seedling growth. Polyvinyl chloride particles were added to potting mix to simulate MP exposure environment (MEE). The results showed that low and medium concentrations (1-4 g kg-1) of MEE had a significant adverse effect on seed germination and seedling growth. In both cases, the germination potential was decreased, young root forks increased, and tips decreased; and the dry weight of seedlings, the total length, surface area, forks and tips of root were also decreased. However, the root activity was increased. The concentration of MEE to give the best parameters was at 2 g kg-1. Catalase enzymatic activity and reactive oxygen species (ROS) in roots were decreased continuously with increased MEE concentrations. The peak values of peroxidase activity, O2.- content and generation rate, ROS enrichment and malondialdehyde content all reached the highest at 2 g kg-1. MEE also increased the proline content and decreased the contents of ascorbic acid, soluble sugar and soluble protein in these seedlings. Medium and high concentrations of MEE (4-8 g kg-1) also increased the chlorophyll b content. Low concentrations MEE (1-2 g kg-1) inhibited actual photochemical efficiency of photosystem II and photochemical quenching, two key chlorophyll fluorescence parameters. Transcriptome analysis showed that the differentially expressed genes caused by the MEE were mainly belonged to defense response, signal transduction, hormone metabolism, plant-pathogen interaction, and phenylpropanoid biosynthesis. The results of this study will help to understand the ecotoxicological effects of MEE on melons and provide data for ecological risk assessment of Cucurbitaceae vegetable cultivation.

Genetically predicted coffee and tea consumption and risk of intracranial aneurysm.

OBJECTIVES: Observational studies have shown associations between coffee and tea consumption and risk of intracranial aneurysm (IA). However, the results are not consistent. We conducted a Mendelian randomization study to clarify whether genetically predicted coffee and tea consumption has a causal effect on IA and its subtypes. METHODS: Genetic variants associated with coffee and tea consumption (cups/day) were obtained from large genome-wide association studies (GWASs), up to 349,376 subjects. Summary-level data for IA were adopted from a GWAS in 79,429 subjects (23 cohorts, 7495 cases, and 71,934 controls). RESULTS: Genetically predicted coffee consumption was associated with a higher risk of any IA and aneurysmal subarachnoid hemorrhage (SAH), but not with unruptured IA. The ORs per 1 cup/day increase in genetically predicted coffee consumption were 1.42 (95% CI: 1.09-1.86; P = 0.010) for IA, 1.51 (95% CI: 1.13-2.03; P = 0.005) for aneurysmal SAH, and 1.20 (95% CI: 0.74-1.96; P = 0.460) for unruptured IA. Genetically predicted tea consumption was not associated with risk of any IA and its subtypes (P > 0.05). The associations remained consistent in sensitivity analyses, and no evidence of pleiotropy was detected. CONCLUSIONS: Our study provides evidence to support that coffee consumption may increase the risk of IA and associated hemorrhage. Coffee should be limited for those at high risk of IA and associated hemorrhage.