Trivalent Phosphine-Catalyzed [4+1] Spiro-annulation Reaction Using Allenyl Imide and Methylene Cyclocompounds.

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.

Hierarchical Hollow TiO2@Bi2WO6 with Light-Driven Excited Bi(3-x)+ Sites for Efficient Photothermal Catalytic CO2 Reduction.

Converting CO2 into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO2 reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO2@Bi2WO6 heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO2@Bi2WO6 photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi(3-x)+ sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 µmol h-1 g-1, which is 15 and 4.7 times higher than that of pure Bi2WO6 and that of physically mixed TiO2/Bi2WO6, respectively. An in situ study shows that the pathway for the transformation of CO2 into CO over our TiO2@Bi2WO6 proceeds via two important intermediates, including COO- and COOH-. Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO2 conversion.

N-Doping Coupled with Co-Vacancies Activating Sulfur Atoms and Narrowing Bandgap for CoS Toward Synergistically Accelerating Hydrogen Evolution.

The combination of hetero-elemental doping and vacancy engineering will be developed as one of the most efficient strategies to design excellent electrocatalysts for hydrogen evolution reaction (HER). Herein, a novel strategy for N-doping coupled with Co-vacancies is demonstrated to precisely activate inert S atoms adjacent to Co-vacancies and significantly improve charge transfer for CoS toward accelerating HER. In this strategy, N-doping favors the presence of Co-vacancies, due to greatly decreasing their formation energy. The as-developed strategy realizes the upshift of S 3p orbitals followed by more overlapping between S 3py and H 1s orbitals, which results in the favorable hydrogen atom adsorption free energy change (ΔGH ) to activate inert S atoms as newborn catalytical sites. Besides, this strategy synergistically decreases the bandgap of CoS, thereby achieving satisfactory electrical conductivity and low charge-transfer resistance for the as-obtained electrocatalysts. With an excellent HER activity of -89.0 mV at 10.0 mA cm-2 in alkaline environments, this work provides a new approach to unlocking inert sites and significantly improving charge transfer toward cobalt-based materials for highly efficient HER.

Engineering Rich Active Sites and Efficient Water Dissociation for Ni-Doped MoS2/CoS2 Hierarchical Structures toward Excellent Alkaline Hydrogen Evolution.

Besides improving charge transfer, there are two key factors, such as increasing active sites and promoting water dissociation, to be deeply investigated to realize high-performance MoS2-based electrocatalysts in alkaline hydrogen evolution reaction (HER). Herein, we have demonstrated the synergistic engineering to realize rich unsaturated sulfur atoms and activated O-H bonds toward the water for Ni-doped MoS2/CoS2 hierarchical structures by an approach to Ni doping coupled with in situ sulfurizing for excellent alkaline HER. In this work, the Ni-doped atoms are evolved into Ni(OH)2 during alkaline HER. Interestingly, the extra unsaturated sulfur atoms will be modulated into MoS2 nanosheets by breaking Ni-S bonds during the formation of Ni(OH)2. On the other hand, the higher the mass of the Ni precursor (mNi) for the fabrication of our samples, the more Ni(OH)2 is evolved, indicating a stronger ability for water dissociation of our samples during alkaline HER. Our results further reveal that regulating mNi is crucial to the HER activity of the as-synthesized samples. By regulating mNi to 0.300 g, a balance between increasing active sites and promoting water dissociation is achieved for the Ni-doped MoS2/CoS2 samples to boost alkaline HER. Consequently, the optimal samples present the highest HER activity among all counterparts, accompanied by reliable long-term stability. This work will promise important applications in the field of electrocatalytic hydrogen evolution in alkaline environments.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

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.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

BACKGROUND: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. METHODS: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. RESULTS: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment. CONCLUSIONS: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Clinical Characteristics and In-Hospital Outcomes of Varying Definitions of Minor Stroke: From a Large-Scale Nation-Wide Longitudinal Registry.

BACKGROUND AND PURPOSE: A variety of definitions for minor stroke have been proposed. We aimed to compare the clinical characteristics and outcomes of minor stroke defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 versus ≤3. METHODS: We retrieved acute ischemic stroke patients with NIHSS score ≤5 in the CSCA study (China Stroke Center Alliance) between August 2015 and 2019. In-hospital clinical outcomes including all-cause mortality, stroke, and myocardial infarction were compared between the NIHSS score ≤5 and NIHSS score ≤3 groups using absolute standardized differences (ASD). RESULTS: A total of 1 006 798 patients were registered in the CSCA program from 1476 hospitals, 472 352 patients had NIHSS score ≤5, of whom 356 314 patients had NIHSS score ≤3. The in-hospital composite events of death, myocardial infarction, or recurrent stroke were not significantly different between the NIHSS score ≤5 and NIHSS score ≤3 groups (5.6% [26 346/472 352] versus 5.2% [18 682/356 314]; ASD, 1.8). The in-hospital all-cause mortality (0.1% [443/472 352] versus 0.1% [255/356 314]; ASD, <0.01), recurrent ischemic stroke (5.3% [25 026/472 352] versus 5.0% [17 777/356 314]; ASD, 1.4), and hemorrhagic stroke (0.5% [2151/472 352] versus 0.4% [1475/356 314]; ASD, 1.5) were not significantly different between both the NIHSS score ≤5 and NIHSS score ≤3 groups. CONCLUSIONS: Our large-scale study identified that minor stroke using NIHSS scores ≤5 and ≤3 as the definition was comparable with each other regarding in-hospital all-cause mortality, recurrent stroke, and hemorrhagic stroke. This observation may be useful for future comparison studies and clinical trial design.

Synergism of rMV-Hu191 with cisplatin to treat gastric cancer by acid sphingomyelinase-mediated apoptosis requiring integrity of lipid raft microdomains.

BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.

Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke.

Background and Purpose- Emergency medical services (EMSs) are critical for early treatment of patients with ischemic stroke, yet data on EMS utilization and its association with timely treatment in China are still limited. Methods- We examined data from the Chinese Stroke Center Alliance for patients with ischemic stroke from June 2015 to June 2018. Absolute standardized difference was used for covariates' balance assessments. We used multivariable logistic models with the generalized estimating equations to account for intrahospital clustering in identifying demographic and clinical factors associated with EMS use as well as in evaluating the association of EMS use with timely treatment. Results- Of the 560 447 patients with ischemic stroke analyzed, only 69 841 (12.5%) were transported by EMS. Multivariable-adjusted results indicated that those with younger age, lower levels of education, less insurance coverage, lower income, lower stroke severity, hypertension, diabetes mellitus, and peripheral vascular disease were less likely to use EMS. However, a history of cardiovascular diseases was associated with increased EMS usage. Compared with self-transport, EMS transport was associated with significantly shorter onset-to-door time, door-to-needle time (if prenotification was sent), earlier arrival (adjusted odds ratio [95% CIs] were 2.07 [1.95-2.20] for onset-to-door time ≤2 hours, 2.32 [2.18-2.47] for onset-to-door time ≤3.5 hours), and more rapid treatment (2.96 [2.88-3.05] for IV-tPA [intravenous recombinant tissue-type plasminogen activator] in eligible patients, 1.70 [1.62-1.77] for treatment with IV-tPA by 3 hours if onset-to-door time ≤2 hours, and 1.76 [1.70-1.83] for treatment with IV-tPA by 4.5 hours if onset-to-door time ≤3.5 hours). Conclusions- Although EMS transportation is associated with substantial reductions in prehospital delay and improved likelihood of early arrival and timely treatment, rate of utilization is currently low among Chinese patients with ischemic stroke. Developing an efficient EMS system and promoting culture-adapted education efforts are necessary for improving EMS activation.

Atrial Fibrillation Known Before or Detected After Stroke Share Similar Risk of Ischemic Stroke Recurrence and Death.

Background and Purpose- We aim to compare the risk of 1-year ischemic stroke recurrence and death for atrial fibrillation diagnosed after stroke (AFDAS), atrial fibrillation known before stroke (KAF), and sinus rhythm (SR). Methods- From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals in the China National Stroke Registry II. Based on heart rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We explored the relationship between heart rhythm groups and 1-year ischemic stroke recurrence or death by using Cox regression adjusted for multiple covariates. Considering that death is a competing risk for stroke recurrence, we used the competing risks analysis of Fine and Gray and subdistribution Cox proportional hazards to test the association between heart rhythm and 1-year outcomes. Results- Among 19 604 ischemic stroke patients, 17 727 had SR, 495 AFDAS, and 1382 KAF. At 1 year, 54 (10.9%) patients with AFDAS, 182 (13.2%) with KAF, and 1008 (5.7%) with SR had recurrent ischemic strokes ( P<0.0001). Mortality was 22.0% in patients with AFDAS, 22.1% in patients with KAF, and 7.0% in patients with SR ( P<0.0001). AFDAS-related ischemic stroke recurrence adjusted risk was higher than that of SR (adjusted subdistribution hazard ratios, 1.61; 95% CI, 1.29-2.01) but not different from that of KAF (adjusted subdistribution hazard ratio, 1.12; 95% CI, 0.87-1.45]). The adjusted risk of 1-year death for AFDAS was also higher than that of SR (hazard ratio, 1.70; 95% CI, 1.37-2.12) and not different from that of KAF (hazard ratio, 1.10; 95% CI, 0.86-1.41). Conclusions- This study showed that AFDAS had similar risk of 1-year ischemic stroke recurrence and mortality when compared with KAF and higher risk when compared with SR. The potential risk of AFDAS should be given more emphasis, and appropriate treatment is needed to achieve reduction in the incidence of stroke recurrence and mortality.

Depression after minor stroke: the association with disability and quality of life--a 1-year follow-up study.

OBJECTIVE: Minor stroke is characterized by mild neurological functional impairment and relatively good outcome. Little is known about the association between post-stroke depression (PSD) and outcomes of minor stroke. The aim of this study was to investigate the association between PSD and disability and quality of life (QoL) at 1 year after minor ischemic stroke. METHODS: Patients with first-ever minor ischemic stroke (n = 747) were followed up at 14 ± 2 days, 3 months, 6 months, and 1 year after stroke. Depressive symptoms were assessed at each follow-up. Patients diagnosed with depression at 14 ± 2 days formed the early-onset PSD group; those who were diagnosed with depression at any subsequent follow-ups for the first time constituted the late-onset PSD group. The outcomes of minor stroke including disability (modified Rankin score ≥ 2) and QoL (Short Form-36 Health Survey) were assessed at the 1-year follow-up. RESULTS: A total of 198 (26.5%) patients were diagnosed with PSD over the 1-year follow-up; 136 and 62 patients were allocated to the early-onset PSD group and late-onset PSD group, respectively. Both early-onset and late-onset PSD were independently associated with disability and poor physical and mental health at 1 year after stroke. Recovery from depression (n = 112) within 1 year decreased the adverse impacts of PSD on functional outcome and QoL. CONCLUSIONS: Post-stroke depression was independently associated with disability and poor QoL at 1 year after first-ever minor ischemic stroke. Recovery from PSD decreased but did not eliminate the adverse impacts of PSD on outcomes of minor stroke.

Symptomatic intracerebral hemorrhage after intravenous thrombolysis in Chinese patients: comparison of prediction models.

BACKGROUND: To assess the performance of risk scores in predicting symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT). METHODS: A multicenter prospective study was performed in 811 patients who underwent IVT with standard-dose recombinant tissue plasminogen activator within 4.5 hours of acute ischemic stroke (AIS) onset in 67 stroke centers involved in the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China program from May 2007 to April 2012. SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age) score, Safe Implementation of Thrombolysis in Stroke (SITS)-SICH score, Glucose Race Age Sex Pressure Stroke Severity (GRASPS) score, Multicenter Stroke Survey (MSS) score, and Stroke Prognostication using Age and National Institutes of Health Stroke Scale (SPAN)-100 index were calculated in selected patients, and their predictive performance for SICH was compared according to the National Institute of Neurological Disorders and Stroke (NINDS), Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), and European Cooperative Acute Stroke Study (ECASS)-II criteria. RESULTS: For predicting the risk of SICH (NINDS definition) after IVT, the area under the receiver operating characteristic (ROC) curve of MSS score was the highest (.71, P < .0001). For predicting the risk of SICH (SITS-MOST definition) after IVT, the area under the ROC curve of GRASPS score was the highest (.73, P = .005). For predicting SICH (ECASS-II definition) after IVT, the area under the ROC curve of MSS score was the highest (.73, P < .0001). CONCLUSIONS: SITS-SICH, GRASPS, and MSS scores predicted the risk of SICH after IVT in patients with AIS, but only the latter 2 were better in the Chinese population. MSS score had the best predictive performance for SICH using NINDS and ECASS-II definitions, whereas GRASPS score was the best for SICH using the SITS-MOST definition.

Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease.

Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells (EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro- and microvasculature.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Engineering surface framework TiO6 single sites for unprecedented deep oxidative desulfurization.

Catalytic oxidative desulfurization (ODS) using titanium silicate catalysts has emerged as an efficient technique for the complete removal of organosulfur compounds from automotive fuels. However, the precise control of highly accessible and stable-framework Ti active sites remains highly challenging. Here we reveal for the first time by using density functional theory calculations that framework hexa-coordinated Ti (TiO6) species of mesoporous titanium silicates are the most active sites for ODS and lead to a lower-energy pathway of ODS. A novel method to achieve highly accessible and homogeneously distributed framework TiO6 active single sites at the mesoporous surface has been developed. Such surface framework TiO6 species exhibit an exceptional ODS performance. A removal of 920 ppm of benzothiophene is achieved at 60°C in 60 min, which is 1.67 times that of the best catalyst reported so far. For bulky molecules such as 4,6-dimethyldibenzothiophene (DMDBT), it takes only 3 min to remove 500 ppm of DMDBT at 60°C with our catalyst, which is five times faster than that with the current best catalyst. Such a catalyst can be easily upscaled and could be used for concrete industrial application in the ODS of bulky organosulfur compounds with minimized energy consumption and high reaction efficiency.

Synergistic effect of K and Zn on Fe-based catalysts for efficient CO2 hydrogenation.

Excessive emission of CO2 into the atmosphere has severely impacted the global ecological environment. Converting CO2 into valuable chemicals and fuels is of great significance for sustainable development. However, low activity and undesirable selectivity often result from the inherent inertness of CO2. Herein, K- or/and Zn-modified Fe-based catalysts were prepared by an incipient-wetness impregnation method for CO2 hydrogenation via a cascade reaction. The results indicate that K species exist as K2O while Zn species exist as ZnFe2O4. In the CO2 hydrogenation pathway, K2O facilitates the adsorption of CO2 and restrains the adsorption of H2, accelerating the transformation of CO2 into C2-C4 olefins rather than paraffins while Zn species promote the dispersion of Fe species, leading to improved activity. Synergistically, a K- and Zn-modified Fe-based catalyst (2Zn-10K-Fe/Al) shows excellent catalytic CO2 hydrogenation activity, achieving a CO2 conversion of 77% which is 1.8 times that (42%) of the unmodified Fe-based catalyst (Fe/Al). Our catalyst also shows a significantly promoted selectivity to C2-C4 olefins of 17% in comparison with the Fe/Al catalyst (0%). It is envisioned that such a binary effect of elements might contribute to the low-cost and industrial production of Fe-based catalysts for selective CO2 conversion.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Perihematomal edema contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors is considerably involved in blood-brain barrier disruption and neuronal cell death in ICH models. We therefore hypothesized that increased levels of these molecular markers are associated with perihematomal edema and clinical outcome in ICH patients. METHODS: Fifty-nine patients with spontaneous ICH admitted within 24 hours of symptom onset were prospectively investigated. Noncontrast CT was performed on admission for diagnosis of ICH and quantification of initial hematoma volume. MRI was performed on day 3 to evaluate perihematomal edema. Concentrations of MMP-3, MMP-9, as well as vascular endothelial growth factor and angiopoietin-1 on admission were determined by enzyme-linked immunosorbent assays. Clinical outcome was assessed by modified Rankin Scale at 90 days. RESULTS: Increased MMP-3 levels were independently associated with perihematomal edema volume (P<0.05). Cytotoxic edema surrounding the hematoma was seen in 36 (61%) cases on 3-day MRI. Cytotoxic edema did not correlate with the level of any of the biomarkers studied. Levels of MMP-3 ≥12.4 ng/mL and MMP-9 ≥192.4 ng/mL but not vascular endothelial growth factor and angiopoietin-1 predicted poor clinical outcome at 90 days (modified Rankin Scale >3) independent of stroke severity and hematoma volume at baseline (odds ratio, 25.3, P=0.035; odds ratio, 68.9, P=0.023; respectively). CONCLUSIONS: MMPs 3 and 9 seem to be significantly involved in secondary brain injury and outcome after primary ICH in humans, and thus should be further evaluated as targets for therapeutic strategies in this devastating disorder.