Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Effects of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene: Mechanisms of secondary organic aerosol formation and cross-dimerization.

Elucidating the mutual effects between the different volatile organic compounds (VOCs) is crucial for comprehending the formation mechanism of atmospheric secondary organic aerosols (SOA). Here, the mixed VOCs experiments of isoprene and Δ3-carene/ß-caryophyllene were carried out in the presence of O3 using an indoor smog chamber. The suppression effect of isoprene was recognized by the scanning mobility particle sizer spectrometer, online vacuum ultraviolet free electron laser (VUV-FEL) photoionization aerosol mass spectrometry, and quantum chemical calculations. The results indicate that the suppression effect of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene shows fluctuating and monotonous trends, respectively. The carbon content of the precursor could be the main factor for regulating the strength of the suppression effect. Plausible structures and formation mechanisms of several new products generated from the single VOC precursor and VOC-cross-reaction are proposed, which enrich the category of VOC oxidation products. Meanwhile, a new dimerization mechanism of the RO2 + R'O2 reaction is suggested, which offers an intriguing perspective on the gas phase formation process of particle phase accretion products. The present findings provide valuable insights into clarifying the pivotal roles played by isoprene in the interplay between different VOCs and understanding of SOA formation mechanisms of VOC mixtures, especially nearby the emission origins.

Advancing anaerobic digestion with MnO2-modified biochar: Insights into performance and mechanisms.

The use of bio-based composites to enhance the methane production in anaerobic digestion has attracted considerable attention. Nevertheless, the study of electron transfer mechanisms and the applications of biochar/MnO2 (MBC) in complex systems remains largely unexplored. Biochar composited with MnO2 at 10:1 mass ratio (MBC10) increased the content of volatile fatty acids by 9.09 % during acidogenic phase. During the methanogenic experiments using acetate, cumulative methane production (CMP) rose by 5.83 %, and in the methanogenic experiments using food waste, CMP increased by 24.32 %. Microbial community analysis indicated an enrichment of Syntrophomonas, Bacilli, and Methanosaetaceae in the MBC10 group. This enrichment occurred mainly due to the redox capability of MnO2 enhancing MBC capacitance, thereby facilitating microbial electron transfer processes. Additionally, under 2 g/L ammonia nitrogen concentration and 30 g/L organic load, the CMP of MBC10 increased by 12.74 % and 9.44 %, respectively, compared to the BC600 group. This study illuminates MBC's electron transfer mechanisms and applications, facilitating its wider practical adoption and fostering future innovations.

Increased peripheral leukocyte aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis: A study based on clinical evidence.

Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100ß, neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100ß), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100ß, and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT.

Exosomal Drug Delivery Systems: A Novel Therapy Targeting PD-1 in Septic-ALI.

BACKGROUND: The cytokine storm triggered by sepsis can lead to the development of acute lung injury (ALI). Human umbilical cord Mesenchymal stem cells derived exosomes (HucMSCs-EXOs) have been demonstrated to possess immunosuppressive and anti-inflammatory properties. Programmed cell death receptor 1 (PD-1) plays a crucial role in maintaining the inflammatory immune homeostasis. The aim of this study is to investigate the synergistic therapeutic effect of EXOs loaded with anti-PD-1 peptide on septic-ALI. METHODS: This study prepares a novel EXOs-based drug, named MEP, by engineering modification of HucMSCs-EXOs, which are non-immunogenic extracellular vesicles, loaded with anti-PD-1 peptide. The therapeutic effect and potential mechanism of MEP on septic-ALI are elucidated through in vivo and in vitro experiments, providing experimental evidence for the treatment of septic acute lung injury with MEP. RESULTS: We found that, compared to individual components (anti-PD-1 peptide or EXOs), MEP treatment can more effectively improve the lung injury index of septic-ALI mice, significantly reduce the expression levels of inflammatory markers CRP and PCT, as well as pro-inflammatory cytokines TNF-α and IL-1ß in serum, decrease lung cell apoptosis, and significantly increase the expression of anti-inflammatory cytokine IL-10 and CD68+ macrophages. In vitro, MEP co-culture promotes the proliferation of CD206+ macrophages, increases the M2/M1 macrophage ratio, and attenuates the inflammatory response. GEO data analysis and qRT-PCR validation show that MEP reduces the expression of inflammasome-related genes and M1 macrophage marker iNOS. CONCLUSION: In both in vitro and in vivo settings, MEP demonstrates superior therapeutic efficacy compared to individual components in the context of septic-ALI.

Voltage mapping and right ventriculography to guide ablation for arrhythmogenic right ventricular cardiomyopathy ventricular tachycardia: a case report.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a family inherited cardiomyopathy associated with ventricular arrhythmias. With the development of molecular biology, histology, imaging, and other diagnostic techniques, the diagnosis rate and incidence of ARVC have gradually increased. However, ARVC remains rare in clinical practice. Currently, the diagnosis and management of ARVC is far from satisfactory in clinical practice. In the case report, we described a clinical case of radiofrequency ablation guided by voltage mapping and right ventriculography in the treatment of ARVC with ventricular tachycardia and discussed the relevant literatures.

NSUN4-mediated m5C modification of circERI3 promotes lung cancer development by altering mitochondrial energy metabolism.

As a highly important methylation modification, the 5-methyladenosine (m5C) modification can profoundly affect RNAs by regulating their transcription, structure and stability. With the continuous development of high-throughput technology, differentially expressed circular RNAs (circRNAs) have been increasingly discovered, and circRNAs play unique roles in tumorigenesis and development. However, the regulatory mechanism of the m5C modification of circRNAs has not yet been revealed. In this study, circERI3, which is highly expressed in lung cancer tissue and significantly correlated with the clinical progression of lung cancer, was initially identified through differential expression profiling of circRNAs. A combined m5C microarray analysis revealed that circERI3 contains the m5C modification and that the NSUN4-mediated m5C modification of circERI3 can increase its nuclear export. The important function of circERI3 in promoting lung cancer progression in vitro and in vivo was clarified. Moreover, we elucidated the novel mechanism by which circERI3 targets DNA binding protein 1 (DDB1), regulates its ubiquitination, enhances its stability, and in turn promotes the transcription of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) through DDB1 to affect mitochondrial function and energy metabolism, which ultimately promotes the development of lung cancer. This study not only revealed the reasons for the abnormal distribution of circERI3 in lung cancer tissues from the perspective of methylation and clarified the important role of circERI3 in lung cancer progression but also described a novel mechanism by which circERI3 promotes lung cancer development through mitochondrial energy metabolism, providing new insights for the study of circRNAs in lung cancer.

Rapid detection of liver metastasis risk in colorectal cancer patients through blood test indicators.

Introduction: Colorectal cancer (CRC) is one of the most common malignancies, with liver metastasis being its most common form of metastasis. The diagnosis of colorectal cancer liver metastasis (CRCLM) mainly relies on imaging techniques and puncture biopsy techniques, but there is no simple and quick early diagnosisof CRCLM. Methods: This study aims to develop a method for rapidly detecting the risk of liver metastasis in CRC patients through blood test indicators based on machine learning (ML) techniques, thereby improving treatment outcomes. To achieve this, blood test indicators from 246 CRC patients and 256 CRCLM patients were collected and analyzed, including routine blood tests, liver function tests, electrolyte tests, renal function tests, glucose determination, cardiac enzyme profiles, blood lipids, and tumor markers. Six commonly used ML models were used for CRC and CRCLM classification and optimized by using a feature selection strategy. Results: The results showed that AdaBoost algorithm can achieve the highest accuracy of 89.3% among the six models, which improved to 91.1% after feature selection strategy, resulting with 20 key markers. Conclusions: The results demonstrate that the combination of machine learning techniques with blood markers is feasible and effective for the rapid diagnosis of CRCLM, significantly im-proving diagnostic ac-curacy and patient prognosis.

Veno-venous extracorporeal membrane oxygenation-assisted treatment of severe airway stenosis due to goiter: Two case reports.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) is a critical care intervention that acts as a temporary substitute for the heart and lungs, facilitating adequate tissue perfusion and gas exchange. The 2 primary configurations, veno-arterial and veno-venous ECMO, are tailored to support either the heart and lungs or the lungs alone, respectively. PATIENT CONCERNS: The case report details patients with tumor-induced airway stenosis who encountered limitations with standard treatments, which were either insufficient or carried the risk of severe complications such as hypoxia and asphyxia. DIAGNOSES: Patients were diagnosed with severe airway stenosis caused by goiter, a condition that required innovative treatment approaches to prevent complications during the management process. INTERVENTIONS: Veno-venous ECMO was implemented as a bridging therapy to provide vital respiratory support during the tumor resection procedure. This intervention was crucial in reducing the risks associated with airway edema or tumor rupture. OUTCOMES: With the use of veno-venous ECMO, the patients successfully underwent tumor resection. They were subsequently weaned off the ECMO support, and after a course of treatment, they were discharged in good condition. LESSONS: The case demonstrates the efficacy of veno-venous ECMO as a bridging therapy for managing severe airway stenosis caused by goiter. Its use facilitated the successful resection of tumors and led to positive patient outcomes, highlighting its potential as a valuable treatment option in similar scenarios.

A Novel Score to Predict Individual Risk for Future Alzheimer's Disease: A Longitudinal Study of the ADNI Cohort.

Background: Identifying high-risk individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer's disease (AD) is crucial for early intervention. Objective: This study aimed to develop and validate a novel clinical score for personalized estimation of MCI-to-AD conversion. Methods: The data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Two-thirds of the MCI patients were randomly assigned to a training cohort (n = 478), and the remaining one-third formed the validation cohort (n = 239). Multivariable logistic regression was performed to identify factors associated with MCI-to-AD progression within 4 years. A prediction score was developed based on the regression coefficients derived from the logistic model and tested in the validation cohort. Results: A lipidomics-signature was obtained that showed a significant association with disease progression. The MCI conversion scoring system (ranged from 0 to 14 points), consisting of the lipidomics-signature and five other significant variables (Apolipoprotein ɛ4, Rey Auditory Verbal Learning Test immediate and delayed recall, Alzheimer's Disease Assessment Scale delayed recall test, Functional Activities Questionnaire, and cortical thickness of the AD signature), was constructed. Higher conversion scores were associated with a higher proportion of patients converting to AD. The scoring system demonstrated good discrimination and calibration in both the training cohort (AUC = 0.879, p of Hosmer-Lemeshow test = 0.597) and the validation cohort (AUC = 0.915, p of Hosmer-Lemeshow test = 0.991). The risk classification achieved excellent sensitivity (0.84) and specificity (0.75). Conclusions: The MCI-to-AD conversion score is a reliable tool for predicting the risk of disease progression in individuals with MCI.

Molecular Insight into the Electric Field Regulation of N2 and CH4 Adsorption in the Trapdoor ZSM-25 Zeolites.

Controlling gas admission by regulating pore accessibility in porous materials has been a topic of extensive research. Recently, the electric field (E-field) has emerged as an external stimulus to alter the adsorption behavior of some microporous adsorbents. However, the mechanism behind this phenomenon is not yet fully understood. Here, we demonstrate the crucial role of the trapdoor cations of zeolite molecular sieves in E-field-regulated gas adsorption. The E-field activation caused framework expansion and cation deviation, significantly reducing the energy barrier for gas molecules passing through the pore aperture gated by the trapdoor cation. This led to an increase in the N2 adsorption capacity of ZSM-25 and a 60% improvement in N2/CH4 selectivity in the quest for nitrogen rejection for natural gas processing. By combining experimental and computational approaches, we elucidated the influence of E-field activation as a concurrent effect of the reduced heat of adsorption caused by framework expansion and the decrease in the energy barrier resulting from promoted cation oscillation. These findings pave the way for the material design of E-field-regulated adsorption and its application in molecular separation.

Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis.

OBJECTIVE: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. METHODS: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected. RESULTS: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride. CONCLUSION: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.

Non-invasive diagnosis of pancreatic steatosis with ultrasound images using deep learning network.

Objective: This study aimed to verify whether pancreatic steatosis (PS) is an independent risk factor for type 2 diabetes mellitus (T2DM). We also developed and validated a deep learning model for the diagnosis of PS using ultrasonography (US) images based on histological classifications. Methods: In this retrospective study, we analysed data from 139 patients who underwent US imaging of the pancreas followed by pancreatic resection at our medical institution. Logistic regression analysis was employed to ascertain the independent predictors of T2DM. The diagnostic efficacy of the deep learning model for PS was assessed using receiver operating characteristic curve analysis and compared with traditional visual assessment methodology in US imaging. Results: The incidence rate of PS in the study cohort was 64.7 %. Logistic regression analysis revealed that age (P = 0.003) and the presence of PS (P = 0.048) were independent factors associated with T2DM. The deep learning model demonstrated robust diagnostic capabilities for PS, with areas under the curve of 0.901 and 0.837, sensitivities of 0.895 and 0.920, specificities of 0.700 and 0.765, accuracies of 0.814 and 0.857, and F1-scores of 0.850 and 0.885 for the training and validation cohorts, respectively. These metrics significantly outperformed those of conventional US imaging (P < 0.001 and P = 0.045, respectively). Conclusion: The deep learning model significantly enhanced the diagnostic accuracy of conventional ultrasound for PS detection. Its high sensitivity could facilitate widespread screening for PS in large populations, aiding in the early identification of individuals at an elevated risk for T2DM in routine clinical practice.

Enantiomer-specific effects of metamifop on serum metabolism in rats.

Metamifop (MET) is a widely used pesticides in paddy field and it has good weed control effect. As a chiral pesticide that may be hazardous to human health through food chain transmission, there could be selective differences in the metabolism and toxicity of its enantiomers, so the study of chiral MET may offer an assessment of MET toxicity and stereoselectivity at the enantiomeric level. A total of 39, 43 and 31 differential metabolites were screened from the data sets of Rac-, R-(-)- and S-(+)-MET, respectively. Metabolic pathway analysis revealed that MET and its enantiomers primarily affected sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, α-linolenic acid metabolism and arachidonic acid metabolism. Rac- and S-(+)-MET affected the synthesis of glycosylphosphatidylinositol (GPI)-anchored biomolecules. R-(-)- and S-(+)-MET affected glutathione metabolism. R-(-)-MET affected vitamin B6 metabolism, selenium compound metabolism, and steroid biosynthesis. Pyrimidine metabolism was only affected by Rac-MET. The experimental results indicated that MET and its enantiomers may affect the nervous and immune systems in rats. Further inter-group difference analysis also demonstrated stereoselectivity of MET and its enantiomers on rat serum metabolism. These findings may provide more detailed information on the toxicity of Rac-, S-(+)- and R-(-)-MET in rat, as well as some context for assessing the environmental risk of the three agents to organisms.

Explore on screening COX-2 inhibitors from the essential oil of Solanum lyratum Thunb. By molecular docking and molecular dynamics simulation.

This study aimed to investigate Solanum lyratum Thunb. with respect to the potential ingredients with anti-inflammatory activity from its essential oil by silico study. To this regard, the essential oil of Solanum lyratum Thunb. was extracted by hydrodistillation. 25 compounds were identified by GC-MS. Using virtual screening, molecular docking and molecular dynamics simulation of the 25 identified compounds, the ones showing anti-inflammatory activity on COX-2 were identified. According to the drug-like principle and the prediction of ADEMT properties, the six compounds of Spathulenol, Cedrol, Juniper camphor, Santalol, Nootkatone and 7,9-Di-tert-butyl-1-oxaspiro[4.5]deca-6,9-diene-2,8-dione were identified and then studied for molecular docking, and based on which the top two compounds of binding free energy were studied by the molecular dynamics simulation. The molecular docking data indicated that the binding free energies of Spathulenol, Cedrol, Juniper camphor, Santalol, Nootkatone and 7,9-Di-tert-butyl-1-oxaspiro[4.5]deca-6,9-diene-2,8-dione to COX-2 protein were -5.65, -7.19, -6.35, -4.94, -5.82 and -5.14 kcal/mol, respectively. The findings showed the steady interactions of hydrogen bonds and hydrophobic bonds between both the top two compounds of binding free energy and the active site residues of COX-2 (4M11) throughout the simulation via hydrogen bonds and hydrophobic bonds. The very study shall be supportive for in vitro and in vivo studies in developing drug products using the lead bioactive ingredients for anti-inflammatory in the future.

Resveratrol promotes diabetic wound healing by inhibiting ferroptosis in vascular endothelial cells.

BACKGROUND: Diabetic wounds are a common complication of diabetes, with alarming disability and mortality rates. Ferroptosis plays an essential role in the occurrence and development of diabetes mellitus and its complications, suggesting that mitigating ferroptosis can be used as a potential therapeutic strategy. Resveratrol (RSV) can promote the angiogenesis of diabetic wounds, but its molecular mechanism is unclear, and RSV has a role in regulating ferroptosis. Therefore, we speculated that RSV could promote the angiogenesis of diabetic wounds and accelerate wound healing by regulating ferroptosis. METHODS: In this study, we investigated the effects of RSV on human umbilical vein endothelial cells (HUVECs) treated with advanced glycation end-products (AGEs), focusing primarily on cell proliferation and markers associated with ferroptosis. The methods employed included the CCK-8 assay for cell proliferation, ROS determination, Fe²âº measurement, scratch and tube formation assays, and transcriptome analysis. To evaluate the effectiveness of RSV in promoting wound healing, we established a type 2 diabetes rat model and created a skin injury model. Wound healing rates were assessed, and tissue samples were analyzed using hematoxylin and eosin (H&E) staining, immunohistochemistry, immunofluorescence, and Western blotting. Additionally, levels of glutathione (GSH) and malondialdehyde (MDA) were measured to evaluate oxidative stress and lipid peroxidation. RESULT: Upon treatment of HUVECs with AGEs, we observed a decrease in cell viability and induction of ferroptosis. RSV can alleviate ferroptosis in AGEs-treated HUVECs. Further investigation through transcriptome analysis and Western blotting revealed that RSV alleviates ferroptosis in AGE-treated HUVECs by modulating the activity of nuclear factor erythroid 2-related factor 2 (Nrf2). In vivo experiments using a diabetic rat skin injury model confirmed that both RSV and Ferrostatin-1 (Fer-1) enhance wound healing and angiogenesis. This effect was associated with the regulation of ferroptosis marker proteins including GPX4, SLC7A11, and ACSL4. Additionally, in the diabetic rat groups treated with RSV and Fer-1, we noted increased expression of Nrf2, vascular endothelial growth factor (VEGF), and CD31 proteins compared to the diabetic rat control group. CONCLUSION: In diabetic wounds, AGEs can lead to ferroptosis in HUVECs. RSV can inhibit AGE-induced ferroptosis in HUVECs, further promoting angiogenesis in diabetic wounds, and ultimately accelerating wound healing.

Accumulation modes and effects of differentially charged polystyrene nano/microplastics in water spinach (Ipomoea aquatica F.).

There is widespread concern about the risk of nano/microplastics (N/MPs) entering the food chain through higher plants. However, the primary factors that influence the absorption of N/MPs by higher plants remain largely unclear. This study examined the impact of Europium-doped N/MPs with different particle sizes and surface charges by water spinach (Ipomoea aquatica F.) to address this knowledge gap. N/MPs were visualized and quantitatively analyzed using laser confocal microscopy, scanning electron microscopy, and inductively coupled plasma-mass spectrometry. N/MPs with different surface charges were absorbed by the roots, with the apoplastic pathway as the major route of transport. After 28 days of exposure to 50 mg L-1 N/MPs, N/MPs-COOH caused the highest levels of oxidative stress and damage to the roots. The plants accumulated NPs-COOH the most (average 1640.16 mg L-1), while they accumulated NPs-NH2 the least (average 253.70 mg L-1). Particle size was the main factor influencing the translocation of N/MPs from the root to the stem, while the Zeta potential mainly influenced particle entry into the roots from the hydroponic solution as well as stem-to-leaf translocation. Different charged N/MPs induced osmotic stress in the roots. A small amount of N/MPs in the leaves significantly stimulated the production of chlorophyll, while excessive N/MPs significantly reduced its content. These results provide new insights into the mechanism of interaction between N/MPs and plants.

Multicentre evaluation of in vitro activity of contezolid against drug-resistant Staphylococcus and Enterococcus.

BACKGROUND: To investigate susceptibility to contezolid, a novel oxazolidinone, multicentre surveillance was conducted involving 2449 strains of Staphylococcus and Enterococcus collected from 65 hospitals across China. METHODS: The MICs of contezolid, linezolid and other clinically significant antibiotics were determined by the broth microdilution method. Consistency with the broth microdilution method for contezolid was assessed using agar dilution method, as well as disc diffusion and ETEST for linezolid, respectively. WGS was conducted on all 20 linezolid-resistant and 30 randomly non-resistant strains to analyse linezolid resistance genes (optrA, poxtA, cfr) and 23S rRNA mutation sites. RESULTS: All strains exhibited WT susceptibility to contezolid, while resistance proportions to daptomycin, vancomycin, teicoplanin, tigecycline and eravacycline ranged from 0% to 5.2% in Staphylococcus, and from 0% to 7.8% in Enterococcus. Linezolid resistance was higher in Enterococcus faecalis (4.4%) compared with Enterococcus faecium (0.2%). Contezolid showed a lower MIC50 (0.5 mg/L) than linezolid (2 mg/L) for methicillin-resistant Staphylococcus. Against Enterococcus, contezolid demonstrated a cumulative MIC percentage of 70% for VRE and 39.1% for E. faecalis (at MIC = 1 mg/L), whereas linezolid showed 0% and 1.1%, respectively. Among the 20 linezolid-resistant Enterococcus strains, all carried the optrA gene without 23S rRNA mutations. For contezolid, MICs were 4 mg/L for 19 strains and 2 mg/L for 1 strain. The ETEST, agar dilution and disc diffusion methods showed essential and categorical agreements of >90% for linezolid, with no major errors or very major errors. CONCLUSIONS: Contezolid demonstrated significant in vitro antibacterial activity against methicillin-resistant Staphylococcus, VRE and linezolid-resistant E. faecalis.

Research on Improved Algorithms for Cone Bucket Detection in Formula Unmanned Competition.

The model network based on YOLOv8 for detecting race cones and buckets in the Formula Unmanned Competition for Chinese university students needs help with problems with complex structure, redundant number of parameters, and computation, significantly affecting detection efficiency. A lightweight detection model based on YOLOv8 is proposed to address these problems. The model includes improving the backbone network, neck network, and detection head, as well as introducing knowledge distillation and other techniques to construct a lightweight model. The specific improvements are as follows: firstly, the backbone network for extracting features is improved by introducing the ADown module in YOLOv9 to replace the convolution module used for downsampling in the YOLOv8 network, and secondly, the FasterBlock in FasterNet network was introduced to replace the fusion module in YOLOv8 C2f, and then the self-developed lightweight detection head was introduced to improve the detection performance while achieving lightweight. Finally, the detection performance was further improved by knowledge distillation. The experimental results on the public dataset FSACOCO show that the improved model's accuracy, recall, and average precision are 92.7%, 84.6%, and 91%, respectively. Compared with the original YOLOv8n detection model, the recall and average precision increase by 2.7 and 1.2 percentage points, the memory is half the original, and the model computation is 51%. The model significantly reduces the misdetection and leakage of conical buckets in real-vehicle tests and, at the same time, ensures the detection speed to satisfy the deployment requirements on tiny devices. Satisfies all the requirements for deployment of tiny devices in the race car of the China University Student Driverless Formula Competition. The improved method in this paper can be applied to conebucket detection in complex scenarios, and the improved idea can be carried over to the detection of other small targets.

Generalizing Treatment Effect to a Target Population Without Individual Patient Data in a Real-World Setting.

The innovative use of real-world data (RWD) can answer questions that cannot be addressed using data from randomized clinical trials (RCTs). While the sponsors of RCTs have a central database containing all individual patient data (IPD) collected from trials, analysts of RWD face a challenge: regulations on patient privacy make access to IPD from all regions logistically prohibitive. In this research, we propose a double inverse probability weighting (DIPW) approach for the analysis sponsor to estimate the population average treatment effect (PATE) for a target population without the need to access IPD. One probability weighting is for achieving comparable distributions in confounders across treatment groups; another probability weighting is for generalizing the result from a subpopulation of patients who have data on the endpoint to the whole target population. The likelihood expressions for propensity scores and the DIPW estimator of the PATE can be written to only rely on regional summary statistics that do not require IPD. Our approach hinges upon the positivity and conditional independency assumptions, prerequisites to most RWD analysis approaches. Simulations are conducted to compare the performances of the proposed method against a modified meta-analysis and a regular meta-analysis.