Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

miRNA-seq provides novel insight into the response to hyper- and hypo- salinity acclimation in Crassostrea hongkongensis.

The Hong Kong oyster, Crassostrea hongkongensis, is a significant bivalve species with economic importance. It primarily inhabits the estuarine intertidal zones in southern China, making it susceptible to salinity fluctuations. Consequently, investigating the molecular mechanisms governing salinity regulation in C. hongkongensis is essential. In this study, we conducted miRNA-seq on C. hongkongensis to compare miRNA expression differences under varying salinities (5‰, 25‰, and 35‰). The miRNA sequencing revealed 51 known miRNAs and 95 novel miRNAs across nine small RNA libraries (S5, S25, and S35). Among these miRNAs, we identified 6 down-regulated differentially expressed (DE) miRNAs in response to hypo-salinity stress (5‰), while 1 up-regulated DE miRNA and 5 down-regulated DE miRNAs were associated with hyper-salinity stress (35‰). Additionally, we predicted 931 and 768 potential target genes for hypo- and hyper-salinity stress, respectively. Functional gene annotation indicated that the target genes under hypo-salinity stress were linked to vesicle-mediated transport and metal ion binding. Conversely, those under hyper-salinity stress were primarily involved in signal transduction and metabolic processes. These findings have provided insights into the regulatory role of miRNAs, their potential target genes and associated pathways in oyster hypo- and hyper-salinity stress, which establish a foundation for future studies on the roles of miRNAs in salinity acclimation mechanisms in C. hongkongensis.

Amino acid analogues provide multiple plausible pathways to prebiotic peptides.

Prebiotic peptide synthesis has consistently been a prominent topic within the field of the origin of life. While research predominantly centres on the 20 classical amino acids, the synthesis process encounters significant thermodynamic barriers. Consequently, amino acid analogues are being explored as potential building blocks for prebiotic peptide synthesis. This review delves into the pathway of polypeptide formation, identifying specific amino acid analogues that might have existed on early Earth, potentially participating in peptide synthesis and chemical evolution. Moreover, considering the complexity and variability of the environment on early Earth, we propose the plausibility of coevolution between amino acids and their analogues.

Utility of real-time 3D visualization system in the early stage of phacoemulsification training.

AIM: To determine the teaching effects of a real-time three dimensional (3D) visualization system in the operating room for early-stage phacoemulsification training. METHODS: A total of 10 ophthalmology residents of the first-year postgraduate were included. All the residents were novices to cataract surgery. Real-time cataract surgical observations were performed using a custom-built 3D visualization system. The training lasted 4wk (32h) in all. A modified International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR) containing 4 specific steps of cataract surgery was applied. The self-assessment (self) and expert-assessment (expert) were performed through the microsurgical attempts in the wet lab for each participant. RESULTS: Compared with pre-training assessments (self 3.2±0.8, expert 2.5±0.6), the overall mean scores of post-training (self 5.2±0.4, expert 4.7±0.6) were significantly improved after real-time observation training of 3D visualization system (P<0.05). Scores of 4 surgical items were significantly improved both self and expert assessment after training (P<0.05). CONCLUSION: The 3D observation training provides novice ophthalmic residents with a better understanding of intraocular microsurgical techniques. It is a useful tool to improve teaching efficiency of surgical education.

Biomechanical Effect of Different Posterior Fixation Techniques on Stability and Adjacent Segment Degeneration in Treating Thoracolumbar Burst Fracture With Osteoporosis: A Finite Element Analysis.

STUDY DESIGN: Finite element analysis. OBJECTIVE: To investigate the biomechanical effect of four posterior fixation tcehniques on stability and adjacent segment degeneration in treating thoracolumbar burst fractures with osteoporosis. SUMMARY OF BACKGROUND DATA: In terms of stability and adjacent segment degeneration, there remains no consensus or guidelines on the optimal technique for the treatment of thoracolumbar burst fractures in patients with osteoporosis. METHODS: Images of CT scans were imported into MIMICS and further processed by Geomagic to build 3-dimensional models of the T10-L5 region. A v-shaped osteotomy was performed on the L1 vertebral body to simulate a burst fracture in the setting of osteoporosis. Subsequently, four fixation techniques were designed using SolidWorks software. Range of motion (ROM) of the global spine, ROM distribution, ROM of adjacent segment, Von Mises stress on adjacent intervertebral discs and facet joints were analyzed. RESULTS: Among the four groups, the cortical bone screw fixation (CBT) showed the highest global ROM at 1.86°, while long-segmented pedicle screw fixation (LSPS) had the lowest global ROM at 1.25°. The LSPS had the smallest percentage of ROM of fractured vertebral body to fixed segment at 75.04%, suggesting the highest stability after fixation. The maximum ROM of the adjacent segment was observed in the CBT at 1.32°, while the LSPS exhibited the smallest at 0.89°. However, the LSPS group experienced larger maximum stress on the adjacent intervertebral discs (9.60MPa) and facet joints (3.36MPa), indicating an increasing risk of adjacent segment disease. CONCLUSION: LSPS provided the greatest stability, while CBT provided the smallest amount of stability. However, the elevated stress on adjacent intervertebral discs and facet joints after LSPS fixation increased the possibility of adjacent segment degeneration. Cement-augmented pedicle screw fixation (CAS) and combined cortical bone screw and pedicle screw fixation (CBT-PS) demonstrated significant biomechanical advantages in providing moderate fixation strength while reducing stress on the intervertebral discs and facet joints.

Multistage Competitive Opinion Maximization With Q-Learning-Based Method in Social Networks.

Competitive opinion maximization (COM) aims to determine some individuals (i.e., seed nodes) from social networks, propagating the desired opinions toward a target entity to their neighbors through social relationships when facing with its competitors (components) and maximize the opinion spread after the specific time. Current studies on COM are still in its infancy, while the only work merely considers the scenario that the strategy of competitors is known but ignores the unknown scenario. In addition, previous studies on COM cannot easily address the situation where some users might dynamically change their opinions. To address the COM issue, we investigate the multistage COM and propose a brand-new Q-learning-based opinion maximization framework (QOMF). Our QOMF consists of two components: dynamic opinion propagation and seeding process. We formulate the COM problem by maximizing relative effective opinions. To produce a dynamic opinion series more realistically, we design an opinion propagation model by joining the activation process and a dynamic opinion process. Moreover, we also verify that the opinion propagation model can reach convergence within finite iterations. To acquire the seed nodes, we design a multistage Q-learning seeding scheme by considering known and unknown competitor strategies, respectively. Experimental results on three real datasets demonstrate that the proposed method outperforms the benchmarks on reaching relatively effective opinions.

Response of anammox consortia to inhibition from high ferroferric oxide nanoparticles concentration and potential recovery mechanism.

The substantial discharge of ferroferric oxide nanoparticles (Fe3O4 NPs) into sewage threatens the survival of functional microorganisms in wastewater treatment. This study elucidated responses of anaerobic ammonium oxidation (anammox) consortia to inhibition from high Fe3O4 NPs concentration and recovery mechanisms. The nitrogen removal efficiency decreased by 20.3 % and recovered after 55 days under 1000 mg/L Fe3O4 NPs concentration. Toxicity was attributed to reactive oxygen species (ROS) production. The excessive ROS damaged membrane integrity, nitrogen metabolism, and DNA synthesis, resulting in the inhibition of anammox bacteria activity. However, recovery mechanisms of anammox consortia activity were activated in response to 1000 mg/L Fe3O4 NPs. The increase of heme oxygenase-1, thioredoxin, and nicotinamide adenine dinucleotide-quinone oxidoreductase genes alleviated oxidative stress. Furthermore, the activation of metabolic processes associated with membrane and DNA repair promoted recovery of anammox bacteria activity. This study provided new insights into NPs contamination and control strategies during anammox process.

A head-to-head comparison of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in patients with nasopharyngeal carcinoma: a single-center, prospective study.

PURPOSE: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. METHODS: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. RESULTS: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. CONCLUSION: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging.

A nomogram combining prognostic nutritional index and platelet lymphocyte ratio predicts postoperative pulmonary infection following D2 radical gastrectomy for gastric cancer.

INTRODUCTION: the prognostic nutritional index (PNI) and platelet-lymphocyte ratio (PLR) have been found to correlate with outcomes following radical gastrectomy for gastric cancer (GC). OBJECTIVES: to construct a nomogram combining PNI and PLR for individually forecasting the risk of postoperative pulmonary infection (POI) following D2 radical gastrectomy for GC. METHODS: retrospectively, clinical data was gathered from 404 patients treated with D2 radical gastrectomy for GC. The study used multivariate logistic regression analysis to screen independent risk factors for POI after surgery. Subsequently, a nomogram was developed based on the above factors to forecast the POI probability accurately. RESULTS: the multivariate logistic regression analysis identified age, PNI, PLR, CA199 level, ASA score, and ICU treatment as independent risk variables for POI following D2 radical gastrectomy (p < 0.001 or 0.05). The nomogram's area under the receiver operating characteristic curve (AUC) for predicting the risk of POI was 0.736 (95 % confidence interval (CI) = 0.678-0.794). The nomogram was internally validated using the bootstrap approach, involving repeated sampling 1000 times. The result yielded a concordance index (c-index) of 0.707 (95 % CI = 0.705-0.709). The calibration curves demonstrated an excellent concordance between the predicted values of the nomogram and the observed values. The nomogram's clinical value was shown to be high using decision analysis curves. CONCLUSIONS: a nomogram combining PNI and PLR is a dependable tool for forecasting the probability of POI following D2 radical gastrectomy for GC.

Numerical Simulation on Radon Retardation Behavior of Covering Floats in Radon-Containing Water.

Objective: This study aimed to efficiently reduce the release of radon from water bodies to protect the environment. Methods: Based on the sizes of the experimental setup and modular float, computational fluid dynamics (CFD) was used to assess the impact of the area coverage rate, immersion depth, diffusion coefficient, and radon transfer velocity at the gas-liquid interface on radon migration and exhalation of radon-containing water. Based on the numerical simulation results, an estimation model for the radon retardation rate was constructed. The effectiveness of the CFD simulation was evaluated by comparing the experimental and simulated variation values of the radon retardation rate with the coverage area rates. Results: The effect of radon transfer velocity on radon retardation in water bodies was minor and insignificant according to the appropriate value; therefore, an estimation model of the radon retardation rate of the coverage of a radon-containing water body was constructed using the synergistic impacts of three factors: area coverage rate, immersion depth, and diffusion coefficient. The deviation between the experimental and simulated results was < 4.3%. Conclusion: Based on the numerical simulation conditions, an estimation model of the radon retardation rate of covering floats in water bodies under the synergistic effect of multiple factors was obtained, which provides a reference for designing covering floats for radon retardation in radon-containing water.

CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

Diagnostic performance of acoustic radiation force impulse for acute pancreatitis: A meta-analysis.

OBJECTIVE: The objective of this meta-analysis is to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) in acute pancreatitis (AP) patients. METHODS: PubMed, Web of Science, Embase, Wanfang, Chinese Biological Medicine databases, and Chinese Biomedical Literature Service System were searched for relevant studies to explore the potential diagnostic performance of ARFI in AP from inception to November 2023. STATA 14.0 was used to analyze the standardized mean difference (SMD) with 95% confidence interval (CI), pooled sensitivity, specificity, area under the curve, meta-regression analysis, sensitivity analysis, and publication bias. RESULTS: Nine studies, involving 533 AP patients and 585 healthy controls, were included. AP patients had significantly higher ARFI levels than healthy controls (SMD: 3.13, 95% CI: 1.88-4.39, P = .001). The area under the curve of ARFI for diagnosing AP was 0.99 (95% CI: 0.98-1.00), with 98% sensitivity and 94% specificity. Meta-regression identified the study region and study period as the sources of heterogeneity. Sensitivity analysis showed that the exclusion of any single study did not materially alter the overall combined effect. No evidence of publication bias was observed in the included studies. CONCLUSION: This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in AP.

Synthesis and Application of Salicylhydrazone Probes with High Selectivity for Rapid Detection of Cu2.

Using the aldehyde amine condensation procedure and the triphenylamine group as the skeleton structure, the new triphenylamine-aromatic aldehyde-succinylhydrazone probe molecule DHBYMH was created. A newly created acylhydrazone probe was structurally characterized by mass spectrometry (MS), NMR, and infrared spectroscopy (FTIR). Fluorescence and UV spectroscopy were used to examine DHBYMH's sensing capabilities for metal ions. Notably, DHBYMH achieved a detection limit of 1.62 × 10-7 M by demonstrating exceptional selectivity and sensitivity towards Cu2+ ions in an optimum sample solvent system (DMSO/H2O, (v/v = 7/3); pH = 7.0; cysteine (Cys) concentration: 1 × 10-4 M). NMR titration, high-resolution mass spectrometry analysis, and DFT computation were used to clarify the response mechanism. Ultimately, predicated on DHBYMH's reversible identification of Cu2+ ions in the presence of EDTA, a molecular logic gate was successfully designed.

Construction of Prediction Model of Foodborne Disease Outbreaks and Its Trend Prediction - Guizhou Province, China, 2023-2025.

Objective: Foodborne diseases pose a significant public health concern globally. This study aims to analyze the correlation between disease prevalence and climatic conditions, forecast the pattern of foodborne disease outbreaks, and offer insights for effective prevention and control strategies and optimizing health resource allocation policies in Guizhou Province. Methods: This study utilized the χ2 test and four comprehensive prediction models to analyze foodborne disease outbreaks recorded in the Guizhou Foodborne Disease Outbreak system between 2012 and 2022. The best-performing model was chosen to forecast the trend of foodborne disease outbreaks in Guizhou Province, 2023-2025. Results: Significant variations were observed in the incidence of foodborne disease outbreaks in Guizhou Province concerning various meteorological factors (all P≤0.05). Among all models, the SARIMA-ARIMAX combined model demonstrated the most accurate predictive performance (RMSE: Prophet model=67.645, SARIMA model=3.953, ARIMAX model=26.544, SARIMA-ARIMAX model=26.196; MAPE: Prophet model=42.357%, SARIMA model=37.740%, ARIMAX model=15.289%, SARIMA-ARIMAX model=13.961%). Conclusion: The analysis indicates that foodborne disease outbreaks in Guizhou Province demonstrate distinct seasonal patterns. It is recommended to concentrate prevention efforts during peak periods. The SARIMA-ARIMAX hybrid model enhances the precision of monthly forecasts for foodborne disease outbreaks, offering valuable insights for future prevention and control strategies.

Multiple extreme overdose of antipsychotics with minimal side effects: A case report.

Key Clinical Message: Antipsychotic drug treatment is a commonly used therapeutic strategy in the field of psychiatry. Rational and standardized use of antipsychotics is crucial in clinical practice, and excessive use of antipsychotics may lead to severe toxic reactions. Thus, attention should be given to the monitoring of drug concentration and examination of organ function. Abstract: Excessive use of antipsychotics can cause a variety of adverse effects, including dysfunction of the liver and other organs. Liver cytochrome P450 (CYP450) enzymes play an important role in the metabolism of antipsychotics, and metabolizer types of CYP450 enzymes may influence the therapeutic effects. In this case report, we introduced a 52-year-old woman with a 23-year history of schizophrenia who took excessive doses of multiple antipsychotics and other herbal preparations for nearly 2 years, with poor response to treatment and minor side reactions to the antipsychotics. Pharmacogenomic examination showed that this patient was a CYP1A2 ultra-rapid metabolizer. The examination and treatment of this patient may provide a reference for the management of similar cases with poor response to an alarming tolerance for antipsychotics.

Antiphospholipid antibody-related hepatic vasculitis in a juvenile after non-severe COVID-19: a case report and literature review.

Antiphospholipid antibodies (aPL) are both laboratory evidence and causative factors for a broad spectrum of clinical manifestations of antiphospholipid syndrome (APS), with thrombotic and obstetric events being the most prevalent. Despite the aPL-triggered vasculopathy nature of APS, vasculitic-like manifestations rarely exist in APS and mainly appear associated with other concurrent connective tissue diseases like systemic lupus erythematous. Several studies have characterized pulmonary capillaritis related to pathogenic aPL, suggesting vasculitis as a potential associated non-thrombotic manifestation. Here, we describe a 15-year-old girl who develops hepatic infarction in the presence of highly positive aPL, temporally related to prior non-severe COVID-19 infection. aPL-related hepatic vasculitis, which has not been reported before, contributes to liver ischemic necrosis. Immunosuppression therapy brings about favorable outcomes. Our case together with retrieved literature provides supportive evidence for aPL-related vasculitis, extending the spectrum of vascular changes raised by pathogenic aPL. Differentiation between thrombotic and vasculitic forms of vascular lesions is essential for appropriate therapeutic decision to include additional immunosuppression therapy. We also perform a systematic review to characterize the prevalence and clinical features of new-onset APS and APS relapses after COVID-19 for the first time, indicating the pathogenicity of aPL in a subset of COVID-19 patients.