Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Transfer learning-based English translation text classification in a multimedia network environment.

In recent years, with the rapid development of the Internet and multimedia technology, English translation text classification has played an important role in various industries. However, English translation remains a complex and difficult problem. Seeking an efficient and accurate English translation method has become an urgent problem to be solved. The study first elucidated the possibility of the development of transfer learning technology in multimedia environments, which was recognized. Then, previous research on this issue, as well as the Bidirectional Encoder Representations from Transformers (BERT) model, the attention mechanism and bidirectional long short-term memory (Att-BILSTM) model, and the transfer learning based cross domain model (TLCM) and their theoretical foundations, were comprehensively explained. Through the application of transfer learning in multimedia network technology, we deconstructed and integrated these methods. A new text classification technology fusion model, the BATCL transfer learning model, has been established. We analyzed its requirements and label classification methods, proposed a data preprocessing method, and completed experiments to analyze different influencing factors. The research results indicate that the classification system obtained from the study has a similar trend to the BERT model at the macro level, and the classification method proposed in this study can surpass the BERT model by up to 28%. The classification accuracy of the Att-BILSTM model improves over time, but it does not exceed the classification accuracy of the method proposed in this study. This study not only helps to improve the accuracy of English translation, but also enhances the efficiency of machine learning algorithms, providing a new approach for solving English translation problems.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation.

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

Preparation and properties of phase-change materials with enhanced radial thermal conductivities based on anisotropic graphene aerogels.

In this study, anisotropic graphene aerogels are prepared using the heat-flow method. Then, graphene aerogels with nanosilver particles are prepared via a silver mirror reaction. The aerogels are soaked in paraffin wax and the effects on the properties of the wax are investigated. The thermal conductivity of pure paraffin wax is 0.2553 W m-1 K-1. For the prepared PCM, the aerogel content was 0.92 vol%; this increases to 1.2234 W m-1 K-1, which corresponds to a thermal conductivity enhancement efficiency of 582%. The axial thermal conductivity is 1.4953 W m-1 K-1, which corresponds to a thermal conductivity enhancement efficiency of 746%. The graphene aerogels with the nanosilver particles show high phase-change efficiency. Owing to the significant improvements in the axial and thermal conductivities, the radial and axial heat transfer properties show good consistency suitable for practical applications.

Extraction of eutrophic and green ponds from segmentation of high-resolution imagery based on the EAF-Unet algorithm.

Inland ponds exhibit remarkable ubiquity across the globe, playing a vital role in the sustainability of global continental freshwater resources and contributing significantly to their biodiversity. Numerous ponds are eutrophic and experience recurrent seasonal or year-round algal blooms or persistent duckweed cover, conferring a characteristic green hue. Here, we denote these eutrophic and green ponds as EGPs. The excessive proliferation of algal blooms and duckweed within these EGPs poses a significant threat to the ecological functioning of these aquatic systems, which can lead to hypoxia or the release of microcystins. To identify these EGPs automatically, we constructed an Efficient Attention Fusion Unet (EAF-Unet) algorithm using Gaofen-2 (GF2) panchromatic and multispectral imagery. The attention mechanism was incorporated in Unet to help better detect EGPs. Using the first EGP labeled dataset, we determined the best input feature combination (RGB, NIR, NDVI, and Bright) and the most effective encoding (Rasnet50) for EAF-Unet for distinguishing EGPs from other ground cover types. The evaluation indices - Precision (0.81), Recall (0.79), F1-Score (0.80), and Intersection over Union (IoU, 0.67) - indicate that EAF-Unet can accurately and robustly extract EGPs from GF2 images without relying on pond water masks. Remote-sensing EGP products can assist in identifying ponds with severe eutrophication. Moreover, these products can serve as references for identifying high-risk areas prone to improper sewage discharge or inadequate sewer construction.

Activated Drp1 Initiates the Formation of Endoplasmic Reticulum-Mitochondrial Contacts via Shrm4-Mediated Actin Bundling.

Excessive mitochondrial fission following ischemia and hypoxia relies on the formation of contacts between the endoplasmic reticulum and mitochondria (ER-Mito); however, the specific mechanisms behind this process remain unclear. Confocal microscopy and time course recording are used to investigate how ischemia and hypoxia affect the activation of dynamin-related protein 1 (Drp1), a protein central to mitochondrial dynamics, ER-Mito interactions, and the consequences of modifying the expression of Drp1, shroom (Shrm) 4, and inverted formin (INF) 2 on ER-Mito contact establishment. Both Drp1 activation and ER-Mito contact initiation cause excessive mitochondrial fission and dysfunction under ischemic-hypoxic conditions. The activated form of Drp1 aids in ER-Mito contact initiation by recruiting Shrm4 and promoting actin bundling between the ER and mitochondria. This process relies on the structural interplay between INF2 and scattered F-actin on the ER. This study uncovers new roles of cytoplasmic Drp1, providing valuable insights for devising strategies to manage mitochondrial imbalances in the context of ischemic-hypoxic injury.

Design, Synthesis, Antitumour Evaluation, and In Silico Studies of Pyrazolo-[1,5-c]quinazolinone Derivatives Targeting Potential Cyclin-Dependent Kinases.

An efficient, straightforward, and metal-free methodology to rapidly access functionalised pyrazolo-[1,5-c]quinazolinones via a [3 + 2] dipolar cycloaddition and regioselective ring expansion process was developed. The synthesised compounds were characterised by methods such as NMR, HRMS, and HPLC. The in vitro antiproliferative activity against A549 cells (non-small cell lung cancer) was significant for compounds 4i, 4m, and 4n with IC50 values of 17.0, 14.2, and 18.1 µM, respectively. In particular, compounds 4t and 4n showed inhibitory activity against CDK9/2. Predicted biological target and molecular modelling studies suggest that the compound 4t may target CDKs for antitumour effects. The synthesised derivatives were considered to have moderate drug-likeness and sufficient safety in silico. In summary, a series of pyrazolo-[1,5-c]quinazolinone derivatives with antitumour activity is reported for the first time. We provide not only a simple and efficient synthetic method but also helpful lead compounds for the further development of novel cyclin-dependent kinase (CDK) inhibitors.

Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.

Background: The strategy of dual blockade of TGF-ß and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFß1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.

Assessing resource allocation based on workload: a data envelopment analysis study on clinical departments in a class a tertiary public hospital in China.

OBJECTIVE: Today, the development mode of public hospitals in China is turning from expansion to efficiency, and the management mode is turning from extensive to refined. This study aims to evaluate the efficiency of clinical departments in a Chinese class A tertiary public hospital (Hospital M) to analyze the allocation of hospital resources among these departments providing a reference for the hospital management. METHODS: The hospitalization data of inpatients from 32 clinical departments of Hospital M in 2021 are extracted from the hospital information system (HIS), and a dataset containing 38,147 inpatients is got using stratified sampling. Considering the non-homogeneity of clinical departments, the 38,147 patients are clustered using the K-means algorithm based on workload-related data labels including inpatient days, intensive care workload index, nursing workload index, and operation workload index, so that the medical resource consumption of inpatients from non-homogeneous clinical departments can be transformed into the homogeneous workload of medical staff. Taking the numbers of doctors, nurses, and beds as input indicators, and the numbers of inpatients assigned to certain clusters as output indicators, an input-oriented BCC model is built named the workload-based DEA model. Meanwhile, a control DEA model with the number of inpatients and medical revenue as output indicators is built, and the outputs of the two models are compared and analyzed. RESULTS: Clustering of 38,147 patients into 3 categories is of better interpretability. 14 departments reach DEA efficient in the workload-based DEA model, 10 reach DEA efficient in the control DEA model, and 8 reach DEA efficient in both models. The workload-based DEA model gives a relatively rational judge on the increase of income brought by scale expansion, and evaluates some special departments like Critical Care Medicine Dept., Geriatrics Dept. and Rehabilitation Medicine Dept. more properly, which better adapts to the functional orientation of public hospitals in China. CONCLUSION: The design of evaluating the efficiency of non-homogeneous clinical departments with the workload as output proposed in this study is feasible, and provides a new idea to quantify professional medical human resources, which is of practical significance for public hospitals to optimize the layout of resources, to provide real-time guidance on manpower grouping strategies, and to estimate the expected output reasonably.

A Potential Anti-Glioblastoma Compound LH20 Induces Apoptosis and Arrest of Human Glioblastoma Cells via CDK4/6 Inhibition.

Glioblastoma (GBM) is a deadly brain tumor characterized by signaling dysregulation and aberrant cell cycle control. The CDK4/6-Rb axis is dysregulated in approximately 80% of all GBM cases. In this study, the anti-GBM effect of a novel pyrimidin-2-amine, LH20 was evaluated in vitro using the primary GBM cell lines U87MG and U251. GBM cells were administered LH20 at concentrations of 0.1, 1, 4, 8, 10, 20, 100, and 200 µM for 24 and 48 h, and the proliferation rate was evaluated using a CCK8 assay. Migration, apoptosis, and cell cycle were also assessed using a wound healing assay, Annexin V-FITC/PI apoptosis assay, and cell cycle staining, respectively. The targets of LH20 were predicted using SwissTargetPrediction and molecular docking. Western blotting analysis was performed to confirm the anti-GBM mechanism of LH20. We found that at concentrations of 4, 8, and 10 µM, LH20 significantly inhibited the proliferation and migration of U87MG and U251 cells, induced late phase apoptosis, promoted tumor cell necrosis, and arrested the G2/M phase of the cell cycle. LH20 also inhibited CDK4 and CDK6 activities by decreasing the phosphorylation of Rb. Our results suggest LH20 as a potential treatment strategy against GBM.

Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins.

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.

[Unilateral biportal endoscopic discectomy for high-grade migrated lumbar disc herniation].

Objective: To investigate the effectiveness of the unilateral biportal endoscopy (UBE) technique in the treatment of high-grade migrated lumbar disc herniation (LDH). Methods: Between January 2020 and February 2021, 23 cases of high-grade migrated LDH were treated with discectomy via UBE. There were 14 males and 9 females, with a mean age of 48.7 years (range, 32-76 years). All patients had low back and leg pain. The disease duration ranged from 2 months to 7 years (median, 13 months). Lesion segments were L 3, 4 in 2 cases, L 4, 5 in 15 cases, and L 5, S 1 in 6 cases. The operation time, intraoperative blood loss, the time when the patients started to move off the floor, and postoperative complications were recorded. The effectiveness was evaluated using the visual analogue scale (VAS) score, the modified Oswestry disability index (ODI), and the modified MacNab criteria. Results: All operations were completed successfully, and no complication such as dural tear, epidural hematoma, nerve injury, or vascular injury occurred. The operation time ranged from 53 to 96 minutes, with an average of 71.0 minutes. The intraoperative blood loss ranged from 32 to 56 mL, with an average of 39.3 mL. All patients were removed the drainage tube and wore a lumbar brace to move off the floor around 1 to 2 days after operation. All patients were followed up 3-12 months after operation, with an average of 5.7 months. The VAS scores of low back pain and leg pain and the modified ODI at all postoperative time points were lower than those before operation, and the differences were significant ( P<0.05). The differences were significant ( P<0.05) when comparing the above indexes between the time points after operation. At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and 17 cases were excellent, 4 cases were good, and 2 cases were fair, with an excellent and good rate of 91.3%. There was no recurrence of LDH during follow-up. Conclusion: Discectomy via UBE is an effective method for the treatment of high-grade migrated LDH because of its flexibility, clear view, and wide range of intraoperative exploration, which can effectively reduce the risk of residual nucleus pulposus after operation.

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.

The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis.

BACKGROUND: It is well known that sepsis is a prevalent severe disease caused by infection and the treatment strategies are limited. Recently pericyte-derived microvesicles (PMVs) were confirmed to be therapeutic in many diseases, whether PMVs can protect vascular endothelial cell (VEC) injury is unknown. METHODS: Pericytes were extracted from the retina of newly weaned rats, and PMVs were collected after starvation and characterized by flow-cytometry and transmission electron microscopy. First, the effect of PMVs on pulmonary vascular function in septic rats was measured via intravenous administration with HE staining, immunofluorescence, and Elisa analysis. Then, PMVs were co-incubated with VECs in the presence of lipopolysaccharide (LPS), and observed the protective effect of PMVs on VECs. Next, the proteomic analysis and further Gene Ontology (GO) enrichment analysis were performed to analyze the therapeutic mechanism of PMVs, and the angiogenesis-related protein CTGF was highly expressed in PMVs. Finally, by CTGF upregulation and downregulation in PMV, the role of PMV-carried CTGF was investigated. RESULTS: PMVs restored the proliferation and angiogenesis ability of pulmonary VECs, and alleviated pulmonary vascular leakage in septic rats and LPS-stimulated VECs. Further study showed that PMVs delivered CTGF to VECs, and subsequently activated ERK1/2, and increased the phosphorylation of STAT3, thereby improving the function of VECs. The further study found CD44 mediated the absorption and internalization of PMVs to VECs, the anti-CD44 antibody inhibited the protective effect of PMVs. CONCLUSIONS: PMVs may delivery CTGF to VECs, and promote the proliferation and angiogenesis ability by activating the CTGF-ERK1/2-STAT3 axis, thereby protecting pulmonary vascular function in sepsis. The therapeutic effect of PMVs was highly related to CD44-mediated absorption. Video Abstract.

A Defect Detection Method for Rail Surface and Fasteners Based on Deep Convolutional Neural Network.

As a result of long-term pressure from train operations and direct exposure to the natural environment, rails, fasteners, and other components of railway track lines inevitably produce defects, which have a direct impact on the safety of train operations. In this study, a multiobject detection method based on deep convolutional neural network that can achieve nondestructive detection of rail surface and fastener defects is proposed. First, rails and fasteners on the railway track image are localized by the improved YOLOv5 framework. Then, the defect detection model based on Mask R-CNN is utilized to detect the surface defects of the rail and segment the defect area. Finally, the model based on ResNet framework is used to classify the state of the fasteners. To verify the robustness and effectiveness of our proposed method, we conduct experimental tests using the ballast and ballastless railway track images collected from Shijiazhuang-Taiyuan high-speed railway line. Through a variety of evaluation indexes to compare with other methods using deep learning algorithms, experimental results show that our method outperforms others in all stages and enables effective detection of rail surface and fasteners.

Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats.

BACKGROUND: Sepsis is a major cause of death in ICU, and intestinal barrier dysfunction is its important complication, while the treatment is limited. Recently, mesenchymal stem cell-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment; whether MMVs are therapeutic in sepsis induced-intestinal barrier dysfunction is obscure. METHODS: In this study, cecal ligation and puncture-induced sepsis rats and lipopolysaccharide-stimulated intestinal epithelial cells to investigate the effect of MMVs on intestinal barrier dysfunction. MMVs were harvested from mesenchymal stem cells and were injected into sepsis rats, and the intestinal barrier function was measured. Afterward, MMVs were incubated with intestinal epithelial cells, and the effect of MMVs on mitochondrial dynamic balance was measured. Then the expression of mfn1, mfn2, OPA1, and PGC-1α in MMVs were measured by western blot. By upregulation and downregulation of mfn2 and PGC-1α, the role of MMVs in mitochondrial dynamic balance was investigated. Finally, the role of MMV-carried mitochondria in mitochondrial dynamic balance was investigated. RESULTS: MMVs restored the intestinal barrier function by improving mitochondrial dynamic balance and metabolism of mitochondria. Further study revealed that MMVs delivered mfn2 and PGC-1α to intestinal epithelial cells, and promoted mitochondrial fusion and biogenesis, thereby improving mitochondrial dynamic balance. Furthermore, MMVs delivered functional mitochondria to intestinal epithelial cells and enhanced energy metabolism directly. CONCLUSION: MMVs can deliver mfn2, PGC-1α, and functional mitochondria to intestinal epithelial cells, synergistically improve mitochondrial dynamic balance of target cells after sepsis, and restore the mitochondrial function and intestinal barrier function. The study illustrated that MMVs might be a promising strategy for the treatment of sepsis.

Effects of Low Concentration Benzophenone-3 Exposure on the Sex Ratio and Offspring Development of Zebrafish (Danio rerio).

Benzophenone-3 (BP-3) is an important ultraviolet (UV)-screening agent using in cosmetics, however, the associated environmental pollution and the toxicity to organisms, particularly aquatic organisms, cannot be neglected. In this study, the potential risks posed to zebrafish when exposed to environmental residual concentrations of BP-3 were evaluated. Zebrafish embryos (F0) were exposed to 0, 0.056, 2.3, and 38 µg/L BP-3 until 42 days' post-fertilization (dpf). The effects of BP-3 on the sex ratio and gene expression of F0 zebrafish were investigated. In the F1 embryos, cumulative hatching rate, body length, and heartbeats were observed. The result showed that F0 and F1 exposure to concentrations of 0.056 and 38 µg/L BP-3 elicited stronger toxicity at 96 hpf than single generation exposures. Overall, our results provide a new understanding on the effects of low BP-3 concentration chronic exposure on sex ratio and offspring developmental toxicity of the F0 zebrafish.

Different acetonitrile degraders and degrading genes between anaerobic ammonium oxidation and sequencing batch reactor as revealed by stable isotope probing and magnetic-nanoparticle mediated isolation.

Microbial degraders play crucial roles in wastewater treatment processes, but their use is limited as most microbes are yet unculturable. Stable isotope probing (SIP) is a cultivation-independent technique identifying functional-yet-uncultivable microbes in ambient environment, but is unsatisfactory for substrates with low assimilation rate owing to the low isotope incorporation into DNA. In this study, we used acetonitrile as the target low-assimilation chemical in many wastewater treatment plants and attempted to identify the active acetonitrile degraders in the activated sludge, via DNA-SIP and magnetic-nanoparticle mediated isolation (MMI) which is another cultivation-independent approach without the requirement of substrate labeling. The two approaches identified different active acetonitrile degraders in a 3-day short-term anaerobic ammonium oxidation (ANAMMOX). MMI enriched significantly more acetonitrile-degraders than SIP, showing the advantages in identifying the active degraders for low-assimilation substrates. Sequencing batch reactor (SBR, 30-day degradation) helped in more incorporation of 15N-labeled acetonitrile into the active degraders, thus the same acetonitrile-degraders and acetonitrile-degrading genes were identified by SIP and MMI. Different acetonitrile degraders between ANAMMOX and SBR were attributed to the distinct hydrological conditions. Our study for the first time explored the succession of acetonitrile-degraders in wastewater and identified the active acetonitrile-degraders which could be further enriched for enhancing acetonitrile degradation performance. These findings provide new insights into the acetonitrile metabolic process in wastewater treatment plants and offer suggestive conclusions for selecting appropriate treatment strategy in wastewater management.

Endothelial Microvesicles Induce Pulmonary Vascular Leakage and Lung Injury During Sepsis.

Sepsis is a prevalent severe syndrome in clinic. Vascular leakage and lung injury are important pathophysiological processes during sepsis, but the mechanism remains obscure. Microvesicles (MVs) play an essential role in many diseases, while whether MVs participate in vascular leakage and lung injury during sepsis is unknown. Using cecal ligation and puncture induced sepsis rats and lipopolysaccharide stimulated vascular endothelial cells (VECs), the role and the underlying mechanism of endothelial microvesicles (EMVs) in pulmonary vascular leakage and lung injury were observed. The role of MVs from sepsis patients was verified. The results showed that the concentration of MVs in blood was significantly increased after sepsis. MVs from sepsis rats and patients induced apparent pulmonary vascular leakage and lung injury, among which EMVs played the dominant role, in which miR-23b was the key inducing factor in vascular leakage. Furthermore, downregulation and upregulation of miR-23b in EMVs showed that miR-23b mainly targeted on ZO-1 to induce vascular leakage. MVs from sepsis patients induced pulmonary vascular leakage and lung injury in normal rats. Application of classic antidepressants amitriptyline reduced the secretion of EMVs, and alleviated vascular leakage and lung injury. The study suggests that EMVs play an important role in pulmonary vascular leakage and lung injury during sepsis by transferring functional miR-23b. Antagonizing the secretion of EMVs and the miR-23b might be a potential target for the treatment of severe sepsis.