Two-step pyrolytic preparation of biochar for the adsorption study of tetracycline in water.

In this study, cow dung biomass was converted into biochar (BC). BC900 was obtained through one-step pyrolysis at 900 °C, while BC700-900 and BC900-700 were obtained via two-step pyrolysis at temperature ranges of 700-900 °C and 900-700 °C, respectively. The primary objective was to investigate the adsorption performance and application value of BCs for tetracycline (TC) in water. The samples underwent characterization using scanning electron microscopy and mapping analysis, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. Subsequently, the effects of reaction time, adsorbent dosage, temperature, pH, and ionic strength were analyzed. Based on the fitting results of adsorption kinetics, the pyrolytic BCs exhibited a better fit with the pseudo-secondary kinetic model. The adsorption isotherm indicated monolayer adsorption on the surface of the adsorbents, with maximum adsorption capacities of 158.93 mg/g for BC900-700, 150.15 mg/g for BC700-900, and 142.56 mg/g for BC900, respectively. Furthermore, results from simulated wastewater and regeneration experiments demonstrated that BC900-700 exhibited not only excellent adsorption performance in wastewater but also remarkable regeneration capabilities. The two-step pyrolysis BCs in this study displayed a higher adsorption capacity compared to the one-step pyrolysis BCs in practical applications. These findings provide insights for further exploring the adsorption mechanism and optimizing the process.

Diabetes, fasting blood glucose and the efficacy of remote ischaemic conditioning: A secondary analysis of the RICAMIS trial.

AIM: To investigate whether diabetes and fasting blood glucose (FBG) levels affect the efficacy of remote ischaemic conditioning (RIC) using the database included in the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) trial. METHODS: A total of 1707 patients were enrolled in this post hoc study, including 535 patients with diabetes and 1172 without diabetes. Each group was further divided into RIC and control subgroups. The primary outcome was excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 1 at 90 days. The difference in the proportion of patients with excellent functional outcome between the RIC subgroup and control subgroup was compared in diabetic and non-diabetic patients, respectively, and the interactions of treatment assignment with diabetes status and FBG were evaluated. RESULTS: Compared with the control group, RIC produced a significantly higher proportion of patients with excellent functional outcome in the non-diabetic group (70.5% vs. 63.2%; odds ratio [OR] 1.487, 95% confidence interval [CI] 1.134-1.949; P = 0.004), while a similar, but not significant difference was observed in the diabetic group (65.3% vs. 59.8%; OR 1.424, 95% CI 0.978-2.073; P = 0.065). Similar results were observed in patients with normal FBG levels (69.3% vs. 63.7%; OR 1.363, 95% CI 1.011-1.836; P = 0.042) and those with high FBG levels (64.2% vs. 58%; OR 1.550, 95% CI 1.070-2.246; P = 0.02). Furthermore, we did not find an interaction effect of intervention (RIC or control) by different diabetes status or FBG levels on clinical outcomes (P > 0.05 for all). However, diabetes (OR 0.741, 95% CI 0.585-0.938; P = 0.013) and high FBG (OR 0.715, 95% CI 0.553-0.925; P = 0.011) were independently associated with functional outcomes in patients overall. CONCLUSION: Diabetes and FBG levels did not influence the neuroprotective effect of RIC in acute moderate ischaemic stroke, although diabetes and high FBG levels were independently associated with functional outcomes.

New use for Lentinus edodes bran biochar for tetracycline removal.

The abuse of antibiotics poses a threat to the ecological environment and biological health, and how to effectively reduce the residue of tetracycline (TC) in the environment has attracted much attention. In this study, three types of pristine biochar (BCs: PBC300, PBC500, and PBC700) were prepared using agricultural waste shiitake mushroom bran at different pyrolysis temperatures to remove TC from water. The structure and surface chemistry of the adsorbents were characterized using different analytical techniques such as scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. These changes in physicochemical properties improve the adsorption capacity of BC. The PBC300 and PBC500 conform to the Langmuir isothermal adsorption model, while the PBC700 is more compatible with the Freundlich model. According to the fitting results of the Langmuir isotherm model, the maximum saturated adsorption capacities of PBC300, PBC500 and PBC700 for TC were 7.568 mg/g, 14.994 mg/g and 17.684 mg/g, respectively. The correlation coefficients of the pseudo-second-order kinetic models were 0.9882, 0.9882 and 0.9996, respectively, which could well fit the adsorption process of TC by the three BCs, indicating that chemical adsorption was dominant. With the help of machine learning, the relationship between the physicochemical properties of BC and the adsorption capacity of TC was effectively explored. The random forest model was able to fit the adsorption process of BC on TC better. It is expected that this study will guide the rational application of BC in the treatment of TC wastewater.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

Atrial cardiopathy and non-stenotic intracranial complicated atherosclerotic plaque in patients with embolic stroke of undetermined source.

OBJECTIVE: To assess (1) the association between atrial cardiopathy (AC) and non-stenotic intracranial complicated atherosclerotic plaque (NICAP) in patients with embolic stroke of undetermined source (ESUS) or small-vessel disease (SVD), and (2) the performance of previously proposed biomarkers to identify AC as the underlying aetiology in ESUS. METHODS: Based on our high-resolution MRI (HR-MRI) cohort, 403 subjects (243 ESUS and 160 SVD) were enrolled in the final analysis. All patients underwent intracranial HR-MRI to assess the presence of ipsilateral NICAP. Biomarkers of AC (ie, P-wave terminal force in lead V1 (PTFV1) on ECG, N-terminal probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T and left atrial diameter) were collected within 24 hours after admission. RESULTS: Among patients without ipsilateral NICAP, we found an association between the presence of AC (adjusted OR (aOR): 4.76, 95% CI 2.48 to 9.14), increased PTFV1 (aOR: 5.70, 95% CI: 2.43 to 13.39) and NT-proBNP (aOR: 1.65, 95% CI: 1.16 to 2.35) with ESUS. This association was not evident among patients with ipsilateral NICAP. The discrimination between ESUS versus SVD by AC/AC-related biomarkers was significantly improved after excluding ipsilateral NICAP. Similarly, the discrimination between ESUS and SVD by ipsilateral NICAP was notably augmented after excluding AC, PTFV1 and NT-proBNP. INTERPRETATION: AC is more prevalent in patients who had ESUS without ipsilateral NICAP compared with patients with, implying that AC and ipsilateral NICAP are two distinct, competing aetiologies of ESUS. Among the AC biomarkers studied in this analysis, PTFV1 seems to be the most informative.

Adsorption of metolachlor by a novel magnetic illite-biochar and recovery from soil.

In this study, we investigated a highly efficient adsorbent that can be recycled from the soil. Walnut shells were used as raw materials to prepare original ecological biochar (OBC), illite modified biochar (IBC), FeCl3 modified biochar (magnetic biochar; MBC), and illite and FeCl3 modified biochar (IMBC), which were tested as low-cost adsorbents. The agents were used to remove metolachlor (MET) from soil. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, magnetic sensitivity curve analysis, and a series of adsorption experiments were conducted to study the interaction between illite and MBC, and the effect on MET adsorption. Compared with OBC, IMBC had more adsorption sites on the surface. IMBC improved the hole filling effect during the adsorption process. IMBC had more oxygen-containing functional groups and it performed better at removing organic matter through π-π interactions. According to the Langmuir model, the Q0 values for IBC, MBC, and IMBC were 91.74 mg g-1, 107.53 mg g-1, and 129.87 mg g-1, respectively, which were significantly higher than that for OBC (72.99 mg g-1). The response surface model was used to explore the optimal adsorption conditions for IMBC. After three regeneration cycles, the MET adsorption rate with IMBC was still 81.38% and the MET recovery rate was 98.12%. Therefore, IMBC was characterized as an adsorbent with high efficiency, low cost, and good recyclability. In addition, we propose a suitable agricultural system for recovering MBC on site in the field.

CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis.

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT-related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up-regulating the expression of MAP3K2 via sponging miR-1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.

QSAR and molecular docking studies on oxindole derivatives as VEGFR-2 tyrosine kinase inhibitors.

The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 30 oxindole derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis comparative molecular similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated value (R(2)) was 0.987, and the external cross-validated value ([Formula: see text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and [Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking studies were employed to bind the inhibitors into the active site to determine the probable binding conformation. The binding mode obtained by molecular docking was in good agreement with the 3D-QSAR results. Based on the QSAR models and the docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were designed, which showed excellent predicting inhibiting potencies. The result revealed that both QSAR models have good predictive capability to guide the design and structural modification of homologic compounds. It is also helpful for further research and development of new VEGFR-2 tyrosine kinase inhibitors.

Phosphoric acid activation of cow dung biochar for adsorbing enrofloxacin in water: Icing on the cake.

In this study, we used different concentrations of H3PO4 to activate pristine biochar (BC) derived from cow dung (BC and BC modified with phosphoric acid at concentrations of 10% (10P-BC), 30% (30P-BC), and 50% (50P-BC)) in order to obtain cheap, high-performance adsorbents. Brunauer-Emmett-Teller analysis, scanning electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, X-ray photoelectron spectroscopy, organic element composition determination, and other analyses showed that activation with H3PO4 increased the porosity and hydrophilicity compared with the original BC, thereby enhancing the adsorption properties. The Langmuir isotherm model obtained the best fit and the maximum capacities for adsorbing enrofloxacin by BCs were 12.66 mg/g for BC, 51.90 mg/g for 10P-BC, 63.61 mg/g for 30P-BC, and 26.79 mg/g for 50P-BC. The main mechanisms responsible for antibiotic loading on BC were hydrogen bonding, π-π electron donor-acceptor interactions, pore filling, and electrostatic interactions. Calculations of fixed carbon retention before and after pyrolysis, and adsorption showed that activated BC had a good carbon fixation capacity and it was more capable of adsorbing enrofloxacin compared with the original BC, thereby providing a new method for removing organic pollutants from the environment and reducing carbon emissions. The cost efficiency was analyzed using the improved fuzzy comprehensive evaluation model based on the entropy method. Removal efficiency and utilization efficiency indicators were calculated for the different phosphoric acid activated BCs. The pollutant removal efficiencies were better for 10P-BC and 30P-BC, and the optimal removal efficiency was determined for 30P-BC. Given the current global climate change situation, using 10P-BC and 30P-BC could also help to meet China's carbon neutrality goals by reducing emissions of pollutants containing carbon.

Adsorption interactions between typical microplastics and enrofloxacin: Relevant contributions to the mechanism.

Microplastics (MPs) are increasingly contaminating the environment and they can combine with antibiotics as carriers to form complex contaminants. In this study, we systematically investigated the interactions between the antibiotic enrofloxacin (ENR) and MPs comprising polyethylene (PE), polyvinyl chloride (PVC), and polystyrene (PS). Characterization was performed by using conventional techniques and the mechanisms involved in interactions were initially explored based on adsorption kinetics, isotherms, and resolution experiments, and the adsorption capacities of the MPs were determined. In addition, the extended Derjaguin-Landau-Verwey-Overbeek theory was used to investigate the interaction mechanisms. The results showed that the interactions were weaker in strong acidic and alkaline environments, and the interactions were also inhibited at higher salt ion concentrations. The saturation adsorption amounts of ENR on PVC, PE, and PS were 74.63 µg/g, 103.09 µg/g, and 142.86 µg/g, respectively. The interactions between MPs and ENR were dominated by hydrophobic interactions, followed by van der Waals forces and acid-base forces. This study provides new insights into the adsorption behavior of ENR by MPs.

Association of AHSG gene polymorphisms with ischemic stroke in a Han Chinese population.

Previous studies have shown associations of fetuin-A (alpha2-Heremans-Schmid glycoprotein, AHSG) with various disorders, including insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and atherosclerosis. In this study, genotype and allele frequencies of the rs4918 SNP in the AHSG gene were examined in 380 patients with ischemic stroke and 350 healthy controls from a Northern Han Chinese population via the PCR-RFLP technique. Frequencies of the GG genotype and the G allele in AHSG (rs4918) were significantly higher in patients with ischemic stroke or atherosclerotic cerebral infarction than those in the control group (P < 0.05). Logistic regression analysis demonstrated the significance of rs4918 in these patients, after adjustment for confounding factors (P < 0.05). These findings suggest that rs4918 SNPs of the AHSG gene are associated with a risk for ischemic stroke in a Northern Han Chinese population.

Association of nNOS gene polymorphism with ischemic stroke in Han Chinese of North China.

Nitric oxide (NO) is an important messenger molecule and effector molecule. This study aimed to investigate the relation of neuronal nitric oxide synthase (nNOS) gene polymorphism with ischemic stroke in Han Chinese of North China. This was a case-control study. A total of 413 patients with ischemic stroke were recruited from Han Chinese of North China. There were 201 males and 212 females. In addition, 477 healthy subjects served as controls including 224 males and 253 females. Multiplex SNaPshot was employed to detect nNOS gene polymorphism (rs2293050, rs2139733, rs7308402, and rs1483757). Results showed that the rs1483757, rs2139733, and rs2293050 genotypes and allele frequencies were comparable between patients and controls. However, ischemic stroke patients had significantly reduced AG genotype and A allele frequency when compared with controls (P = 0.037, P = 0.041). After adjusting confounding factors (gender, age, smoking, history of drinking, hypertension, and diabetes), AG genotype and A allele were still related to ischemic stroke (OR = 0.572, 95% CI: 0.335-0.978, P = 0.041; OR = 0.611, 95% C: 0.378-0.985, and P = 0.041) and both were found to be protective factors. Our results showed that rs7308402 gene polymorphism of nNOS is related to ischemic stroke in Han Chinese of North China.

Vitamin C modified crayfish shells biochar efficiently remove tetracycline from water: A good medicine for water restoration.

In this study, crayfish shell biochar (CSB) was modified by introducing vitamin C (VC) with abundant surface functional groups. CSB was impregnated with VC at different ratios and its capacity to adsorb tetracycline (TC) from water was analyzed. The physicochemical properties of CSB were determined by N2 adsorption-desorption isotherm analysis, X-ray diffraction, and Fourier transform infrared spectroscopy. The effects of various factors on adsorption such as the pH, TC concentration, time, and salt ion concentrations were also investigated. Based on the chemical structure of VC, VC can provide CSB with more oxygen-containing functional groups such as hydroxyl groups. The results showed that the CSB modified with VC (CSB-VC) exhibited excellent adsorption of TC, and CSB-VC2 with an impregnation ratio of 2 (gVC/gCSB) had the greatest adsorption performance (saturated adsorption capacity, Qm = 293.36 mg/g), whereas the adsorption performance of CSB alone was about 50% lower (Qm = 172.16 mg/g). The optimal impregnation ratio VC improved the adsorption performance of CSB after modification to 70.4% of the original. Hydrogen bonding, p-p conjugation, pi-pi electron donor-acceptor effect, and π-π interactions were identified as the main adsorption mechanisms. CSB-VC2 was highly effective over a wide range of pH values and at high ion concentrations. Experiments demonstrated the effective regeneration of the adsorbent after multiple cycles, thereby indicating its excellent reusability. It should be noted that the adsorption capacity was good under different water quality conditions, and thus it should exhibit stable adsorption performance under complex water environment conditions.

Late-onset cobalamin C deficiency type in adult with cognitive and behavioral disturbances and significant cortical atrophy and cerebellar damage in the MRI: a case report.

Background: Late-onset cobalamin C (cblC) deficiency is associated with a wide range of neurological and psychiatric symptoms, hematological manifestations, anorexia, renal failure, ocular abnormalities, dermatitis, and pancreatitis. However, the neuroimaging characteristics of late-onset cblC deficiency remain insufficiently documented. Common findings include diffuse white matter swelling, varying degrees of severe leukoaraiosis, hydrocephalus, corpus callosum atrophy, and symmetric bilateral basal ganglia lesions. In this report, we present a case of late-onset cblC deficiency in adults presenting with cerebellar ataxia as the primary symptom. The MRI findings revealed bilateral lateral cerebellar hemispheres exhibiting symmetric hyperintensity, primarily observed in diffusion-weighted imaging (DWI), which is a rarely reported imaging change in this context. Case presentation: Our patient was a male who experienced symptoms starting at the age of 30 years, including unsteady walking, apparent cerebellar ataxia, and cognitive impairment upon nervous system examination. Brain magnetic resonance imaging (MRI) exhibited symmetric hyperintensity in the bilateral lateral cerebellar hemispheres, predominantly manifested in DWI, without any enhancement. Subsequently, significantly elevated blood total homocysteine and urinary methylmalonic acid levels were observed. Genetic analysis confirmed the presence of MMACHC compound heterozygous mutants c.482G > A and c.609G > A, thus confirming the diagnosis of cblC deficiency. These variants were classified as likely pathogenic following the guidelines of the American College of Medical Genetics and Genomics (ACMG) and were verified using Sanger sequencing. Following treatment, the patient experienced improvements in walking ability and cognition, a significant decrease in blood total homocysteine levels, and reversal of the imaging lesions. In conclusion: Late-onset cblC deficiency presents with diverse clinical and imaging manifestations. Early diagnosis and treatment are crucial in achieving a favorable prognosis. This case serves as a reminder to clinicians not to overlook genetic metabolic disorders, particularly those causing multisite damage, in adult patients with undiagnosed neurological disorders, especially those affecting the cerebellum. Notably, methylmalonic acidemia should be considered within the spectrum of bilateral cerebellar lesions.

The carrier effect mechanism of butachlor in water by three typical microplastics.

Butachlor (BUT) is a widely used herbicide that can cause environmental problems when used excessively. BUT has been found to exist in large quantities in the water environment so far. As an agricultural pre-emergent herbicide, BUT can enter the water environment through multiple channels and cause pollution. This study investigated the mechanism of three types of microplastics (MPs): polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC) to remove BUT from water. The adsorption behavior between MPs and BUT under different factors, namely pH, salt ion concentration, and aging, was investigated. This study further investigated the desorption and aging of BUT-adsorbed MPs. In this research, the adsorption capacity of BUT by PE, PP, and PVC are 13.65 µg/g, 14.82 µg/g, and 18.88 µg/g, respectively, and the order of carrier effect was: PVC>PP>PE. Experiments show that MPs have low adsorption performance on the microgram level for BUT. The adsorption behavior of PE, PP, and PVC on BUT conformed to pseudo-second-order kinetics, indicating the presence of physical and chemical adsorption. The Langmuir isotherm model fits well, indicating that the adsorption is a single-layer adsorption process. The pH value causes slight fluctuations in the overall carrier effect. Low concentration of salt ions can inhibit the carrier effect, and high concentration will promote the interaction between MPs and BUT. Aging experiments show that the carrier effect of the original materials was higher than the adsorption capacity of hydrogen peroxide and MPs after acid aging, and acid aging can cause the adsorption capacity to drop significantly.

Central pontine myelinolysis: a rare finding in hyperosmolar hyperglycemia.

Central pontine myelinolysis (CPM) is a heterogeneous nervous system disease of pontine demyelination, usually caused by rapid correction of hyponatremia. In the present study, we report a unique case of a 46-year-old man with a hyperglycemic state complicated with CPM. MRI demonstrated a high signal on T2 and symmetric restricted diffusion in the pontine. In conclusion, the clinical case described confirmed that the hyperosmolar state inherent in hyperglycemia was a likely cause of CPM.

Intracranial plaque with large lipid core is associated with embolic stroke of undetermined source.

OBJECTIVE: To investigate an association between percentage lipid-rich necrotic core (LRNC) and an index ischemic stroke in an embolic stroke of undetermined source (ESUS) cohort. METHODS: A total of 167 ESUS patients with 259 non-stenotic intracranial plaques including 155 ipsilateral and 104 contralateral to stroke were finally enrolled in the current analysis. The multi-dimensional parameters involving remodeling index (RI), plaque burden (PB), LRNC, discontinuity of plaque surface (DPS), intraplaque hemorrhage (IPH), and vulnerable plaque defined as presence of complicated plaque were evaluated by high-resolution magnetic resonance imaging. RESULTS: We found that %LRNC was an independent predictor for ESUS in model 1 (OR: 2.574, 95% CI: 1.854-3.573, P < 0.001), and model 2 (OR: 2.550, 95% CI: 1.835-3.545, P < 0.001), but the association was not seen in PB. In receiver operating characteristic curve analysis, the discrimination of LRNC for ESUS was significantly superior to that of PB (absolute difference: 0.121, 95% CI: 0.056-0.205, P < 0.001). Importantly, a significantly positive synergy between the remodeling pattern and LRNC in response to plaque vulnerability was found by Sankey diagram (P for interaction = 0.001). CONCLUSION: This is the first report that LRNC, beyond PB, may be correlated with an index ESUS, and a synergistic effect between positive remodeling and larger LRNC could promote plaque vulnerability. The findings suggest that a potential target subgroup may benefit from stroke prevention with intensive statin, although this must be confirmed in future.

MRI-based risk stratification for recurrent ischemic stroke in embolic stroke of undetermined source.

OBJECTIVE: Leukoaraiosis and other brain MRI-assessed parameters were shown to be associated with recurrent stroke in this population. We aimed to develop an MRI-based predictive tool for risk stratification of ESUS patients. METHODS: We retrospectively assessed consecutive patients who were diagnosed with ESUS and underwent brain MRI and performed a multivariable analysis with the outcome of recurrent stroke/TIA. Based on the coefficient of each covariate, we generated an integer-based point scoring system. The discrimination and calibration of the score were assessed using the area under the receiver operator characteristic curve, net reclassification improvement, integrated discrimination improvement, calibration curve, and decision curve analysis. Also, we compared the new score with a previously published score (ALM score). RESULTS: Among 176 patients followed for an overall period of 902.3 patient-years (median of 74 months), there were 39 recurrent ischemic stroke/TIAs (4.32 per 100 patient-years). Fazekas score (HR: 1.26, 95% CI: 1.03-1.54), enlarged perivascular space (EPVS) (HR: 2.76, 95% CI: 1.12-6.17), NIHSS at admission (HR: 1.11, 95% CI: 1.02-1.18), and infarct subtypes (HR: 2.88, 95% CI: 1.34-6.17) were associated with recurrent stroke/TIA. Accordingly, a score (FENS score) was developed with AUC-ROC values of 0.863, 0.788, and 0.858 for 1, 3, and 5 years, respectively. These were significantly better than the AUC-ROC of ALM score (0.635, 0.695, and 0.705, respectively). The FENS score exhibited better calibration and discrimination ability than the ALM score (Hosmer-Lemeshow test χ2 : 4.402, p = 0.819). CONCLUSION: The MRI-based FENS score can provide excellent predictive performance for recurrent stroke/TIA and may assist in risk stratification of ESUS patients.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5-24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study.

BACKGROUND AND PURPOSE: Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. METHODS: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5-24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0-1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). RESULTS: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46-2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0-2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. CONCLUSION: This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5-24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Tetracycline adsorption mechanisms by NaOH-modified biochar derived from waste Auricularia auricula dregs.

Tetracycline (TC) is not easy to degrade in human or animal and can even be converted to more toxic substances. The overuse and wanton discharge of TC also caused serious problem of water pollution. This study investigated the removal of TC by biochar (BC) prepared from waste Auricularia auricula dregs and modified with NaOH by characterizing the pH and adsorption kinetics, and using isotherm models. Three BC samples were prepared and that produced using the highest concentration of NaOH (8 M) was more suitable for removing TC, where the adsorption amount was 26.65 mg/g. Pseudo-second order and Freundlich models both fitted well to the adsorption kinetics, and diffusion of the liquid film was considered the rate-controlling step. The multivariate mechanism involved electron interplay, H-bonding, and π-π electron donor-acceptor interactions. The results of this work can not only make the waste Auricularia auricula dregs resourceful, but also provide a new method for the removal of TC in wastewater, which is of great practical significance.