Ionized Phenanthroline Derivatives Suppressing Interface Chemical Interactions with Active Layer for High-efficiency Organic Solar Cells with Exceptional Device Stability.

The contact interface between the charge transport interlayer and the active layer is crucial for the non-fullerene organic solar cells (NF OSCs) to achieve high efficiency and long-term stability. In this study, two novel phenanthroline (Phen) derivatives, tbp-Phen and tbp-PhenBr, are developed as efficient cathode interfacial materials (CIMs). The larger steric hindrance substituents and the ionization of nitrogen atoms on the Phen framework jointly enable the tbp-PhenBr CIM with a stable film morphology and immensely suppress the detrimental interface chemical interactions with the NF active layer. Consequently, tbp-PhenBr-based OSC achieves a higher efficiency (PCE = 16.34%) than bathocuproine (BCP)-based control device (PCE = 13.70%) using PM6:Y6 as the active layer. More importantly, the tbp-PhenBr-based device maintains 80% of its initial efficiency (T80) for 3264 h in dark conditions and 220 h after being heated at 85 °C, significantly outperforming the BCP-based device. The tbp-PhenBr CIM also shows broad applicability across various binary and ternary active layer systems, affording a notable PCE of 19.49%. Additionally, the tbp-PhenBr CIM can be processed via a thermal evaporation technique and the prepared devices exhibit high reproducibility. This work provides innovative insights into the molecular design of the CIMs for stable and efficient NF OSCs.

Effect of occlusion site on the effectiveness and safety of endovascular thrombectomy for large ischemic cores: A cohort study.

BACKGROUND: Recent clinical trials have shown that patients with large ischemic cores have better outcomes with endovascular thrombectomy (EVT) compared with standard medical treatment (SMT) alone.We aim to assess whether the relationship between EVT and improvements in clinical outcomes varies depending on the location of the occlusive sites. METHODS: This study is a subgroup analysis conducted within a prospective, nationwide, multi-center registry. The cohort included patients with acute large vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 0 to 5 within 24 hours from last known well. We utilized the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after EVT compared with SMT alone as the primary outcome. Safety outcomes included symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 745 patients with large ischemic cores were included: 272(36.5%) with internal carotid artery occlusion, 392(52.6%) with M1 segment of the middle cerebral artery occlusion, and 81(11.0%) with M2 segment of the middle cerebral artery occlusion. The adjusted common odds ratios were as follows: 1.98 (95% CI, 1.01-3.89) for ICA occlusions, 2.09 (95% CI, 1.35-3.23) for M1 occlusions, and 1.13 (95% CI, 0.43-2.94) for M2 occlusions. There was no significant treatment-by-occlusion site interaction observed (P=0.69). However, the incidence of sICH was significantly greater in all groups receiving EVT than in those receiving SMT alone. Additionally, we observed that the secondary outcomes and subgroup analyses were generally consistent with the main outcomes. CONCLUSIONS: In this study, we found that patients with internal carotid artery and M1 occlusion demonstrated a better outcome with EVT, while the benefit for patients with M2 occlusion remains uncertain.

Impact of stress hyperglycemia on outcomes in patients with large ischemic stroke.

BACKGROUND: Clinical evidence of the potential influence of stress hyperglycemia ratio (SHR) for patients with large ischemic stroke whether or not receiving endovascular therapy is not clear. METHODS: This study was a subanalysis of a prospective, multicenter registry, and included 745 patients with large ischemic stroke across 38 centers in China. A total of 427 patients were included in this study, with 285 received endovascular therapy (EVT) and 142 received standard medical therapy (SMT). SHR was defined as glucose (mmol/L)/(1.59 × HbA1C)-2.59. The primary outcome was a moderate neurological outcome (modified Rankin Scale (mRS) score ≤3) at 90 days. RESULTS: A significant interaction was observed between SHR and whether received EVT (p=0.017). Among patients who received EVT (adjusted OR (aOR) 0.46; 95% CI 0.23 to 0.92; p=0.029), patients in the highest tertile of SHR were significantly less likely to achieve a moderate neurological outcome at 90 days compared with those in the lowest tertile. However, this association was not observed in patients receiving SMT (aOR 2.46; 95% CI 0.74 to 8.21; p=0.142). EVT patients with higher SHR had a significantly higher incidence of symptomatic intracranial hemorrhage compared with lower SHR (aOR 3.29; 95% CI 1.08 to 10.06; p=0.036), while such an association was not observed in the SMT group (aOR 1.52; 95% CI 0.56 to 4.12; p=0.410). CONCLUSIONS: In patients with large ischemic stroke treated with EVT, SHR is associated with a reduced likelihood of achieving a moderate neurological outcome, as well as an increased risk of symptomatic intracranial hemorrhage. TRIAL REGISTRATION NUMBER: ChiCTR2100051664.

Blocking the WNT/ß-catenin pathway in cancer treatment:pharmacological targets and drug therapeutic potential.

The WNT/ß-catenin signaling pathway plays crucial roles in tumorigenesis and relapse, metastasis, drug resistance, and tumor stemness maintenance. In most tumors, the WNT/ß-catenin signaling pathway is often aberrantly activated. The therapeutic usefulness of inhibition of WNT/ß-catenin signaling has been reported to improve the efficiency of different cancer treatments and this inhibition of signaling has been carried out using different methods including pharmacological agents, short interfering RNA (siRNA), and antibodies. Here, we review the WNT-inhibitory effects of some FDA-approved drugs and natural products in cancer treatment and focus on recent progress of the WNT signaling inhibitors in improving the efficiency of chemotherapy, immunotherapy, gene therapy, and physical therapy. We also classified these FDA-approved drugs and natural products according to their structure and physicochemical properties, and introduced briefly their potential mechanisms of inhibiting the WNT signaling pathway. The review provides a comprehensive understanding of inhibitors of WNT/ß-catenin pathway in various cancer therapeutics. This will benefit novel WNT inhibitor development and optimal clinical use of WNT signaling-related drugs in synergistic cancer therapy.

Adjunctive intra-arterial tenecteplase after successful endovascular thrombectomy in patients with large vessel occlusion stroke (POST-TNK): Study rationale and design.

RATIONALE: Adjunct intra-arterial alteplase has been shown to potentially improve clinical outcomes in patients with large vessel occlusion (LVO) stroke who have undergone successful endovascular thrombectomy. Tenecteplase, known for its enhanced fibrin specificity and extended activity duration, could potentially enhance outcomes in stroke patients after successful reperfusion when used as an adjunct intra-arterial therapy. AIM: To explore the safety and efficacy of intra-arterial tenecteplase after successful endovascular thrombectomy in patients with LVO stroke. SAMPLE SIZE: To randomize 498 participants 1:1 to receive intra-arterial tenecteplase or no intra-arterial adjunctive thrombolysis therapy. METHODS AND DESIGN: An investigator-initiated, prospective, randomized, open-label, blind-endpoint multicenter clinical trial. Eligible patients with anterior circulation LVO stroke presenting within 24 h from symptom onset (time last known well) and excellent to complete reperfusion (expanded Thrombolysis In Cerebral Infarction (eTICI) scale 2c-3) at endovascular thrombectomy are planned to be randomized. OUTCOMES: The primary outcome is freedom from disability (modified Rankin Scale, mRS, of 0-1) at 90 days. The primary safety outcomes are mortality through 90 days and symptomatic intracranial hemorrhage within 48 h. DISCUSSION: The POST-TNK trial will evaluate the efficacy and safety of intra-arterial tenecteplase in patients with LVO stroke and excellent to complete reperfusion.

Association of Admission Hyperglycemia with Clinical Outcomes in Patients with Symptomatic Intracranial Hemorrhage After Endovascular Treatment for Large Vessel Occlusive Stroke.

Background: Symptomatic intracranial hemorrhage (sICH) is a fatal complication after endovascular treatment (EVT) for acute large vessel occlusive (LVO) stroke. The aim of this study was to investigate the association between hyperglycemia and outcomes in patients with postprocedural sICH. Methods: Of the 2567 patients with AIS who underwent EVT from two large multicenter randomized trials and two prospective multicenter registry studies, 324 patients occurred sICH with documented admission glucose were included in this study. The primary outcome was functional independence (defined as a modified Rankin Scale score of 0 to 2) at 90 days. Secondary outcomes included mRS score of 0 to 3, 0 to 1, and mRS score at 90 days. Safety outcome was the mortality within 90 days. Admission hyperglycemia was defined as a plasma blood glucose ≥7.8 mmol/L (140 mg/dL) in our analysis. Results: Of 324 eligible participants included in this study, hyperglycemia was observed in 130 (40.1%) patients. The median age was 67 (IQR, 58-75) years, and median blood glucose level was 7.1 (IQR, 6.0-9.3) mmol/L. After adjusting for confounding variables, admission hyperglycemia was associated with decreased odds of functional independence (adjusted odds ratio[OR] 0.34; 95% CI 0.17-0.68; P= 0.003), decreased odds of favorable outcome (adjusted OR 0.31; 95% CI 0.16-0.58; P < 0.001) and increased odds of mortality (adjusted OR 2.56; 95% CI 1.47-4.45; P = 0.001) at 90 days. After 1:1 propensity score matching analysis, the results were consistent with multivariable logistic regression analysis. Conclusion: In patients who suffered sICH after EVT for acute large vessel occlusive stroke, hyperglycemia is a strong predictor of poor clinical outcome and mortality at 90 days.

Safety and efficacy of tirofiban combined with intravenous thrombolysis and endovascular treatment in acute large vessel occlusion stroke.

OBJECTIVE: This study assesses the safety and efficacy of tirofiban for patients with large vessel occlusion stroke after intravenous thrombolysis. METHODS: This study data was from SUSTAIN, DEVT, and RESCUE BT trials. According to whether the use of tirofiban who underwent endovascular treatment and preceding intravenous thrombolysis was divided into the tirofiban group and the no-tirofiban group. The safety outcomes were symptomatic intracranial hemorrhage, any intracranial hemorrhage within 48 h, and 3-month mortality. The efficacy outcome was defined as a score of 0-2 on the modified Rankin Scale scores at 3 months. RESULTS: A total of 372 patients with intravenous thrombolysis were included in these SUSTAIN, DEVT, and RESCUE BT trials. Adjusted multivariate analysis showed that tirofiban with intravenous thrombolysis was not associated with symptomatic intracranial hemorrhage (aOR, 0.87; 95 % CI, 0.49-1.57; P=0.65), any intracranial hemorrhage within 48 h (aOR, 1.00; 95 % CI, 0.60-1.66; P=1.00), 3-month mortality (aOR, 1.10; 95 % CI, 0.56-2.19; P=0.78) and 3-month modified Rankin Scale scores 0-2 (aOR, 0.72; 95 % CI, 0.42-1.25; P=0.25) in patients with acute large vessel occlusion. In the subgroup analysis, we found that tirofiban was not recommended for females (aOR, 0.34; 95 % CI, 0.12-0.93), baseline Alberta Stroke Program Early CT Score≤9 (aOR, 0.37; 95 % CI, 0.18-0.76), and cardiogenic embolism (aOR, 0.36; 95 % CI, 0.14-0.97). CONCLUSION: Tirofiban combined with intravenous thrombolysis in patients with acute large vessel occlusion may be safe. Further studies need to confirm the effectiveness of tirofiban after intravenous thrombolysis in different stroke etiology.

Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

BACKGROUND: In the RESCUE BT (endovascular treatment with versus without tirofiban for stroke patients with large vessel occlusion) trial, enrollment in extended time window was based on noncontrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. METHODS: This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6 h window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48 h and 90-day mortality. RESULTS: A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median interquartile ranges (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% CI: 0.83-1.42). The incidence of sICH [10.1% versus 6.3%; adjusted OR 1.70; (95% CI: 0.95-3.04)] was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level [adjusted common OR, 1.74 (95% CI: 1.14-2.65); P =0.01] in patients with large artery atherosclerosis. CONCLUSIONS: There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. The authors observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

Changes in the state of matter of KCIO4 to improve thermal and combustion properties of Al/MoO3 nanothermite.

To improve the thermal and combustion properties of nanothermites, a design theory of changing the state of matter and structural state of the reactants during reaction was proposed. The Al/MoO3/KClO4 (Kp) nanothermite was prepared and the Al/MoO3 nanothermite was used as a control. SEM and XRD were used to characterize the nanothermites; DSC was used to test thermal properties; and constant volume and open combustion tests were performed to examine their combustion performance. Phase and morphology characterization of the combustion products were performed to reveal the mechanism of the aluminothermic reaction. The results show that the Al/MoO3/Kp nanothermite exhibited excellent thermal properties, with a total heat release of 1976 J·g- 1, increasing by approximately 33% of 1486 J·g- 1 of the Al/MoO3 nanothermite, and activation energy of 269.66 kJ·mol- 1, which demonstrated higher stability than the Al/MoO3 nanothermite (205.64 kJ·mol- 1). During the combustion test, the peak pressure of the Al/MoO3/Kp nanothermite was 0.751 MPa, and the average pressure rise rate was 25.03 MPa·s- 1, much higher than 0.188 MPa and 6.27 MPa·s- 1 of the Al/MoO3 nanothermite. The combustion products of Al/MoO3 nanothermite were Al2O3, MoO, and Mo, indicating insufficient combustion and incomplete reaction, whereas, the combustion products of Al/MoO3/Kp nanothermite were Al2O3, MoO, and KCl, indicating complete reaction. Their "coral-like" morphology was the effect of reactants solidifying after melting during the combustion process. The characterization of reactants and pressure test during combustion reveals the three stages of aluminothermic reaction in thermites. The excellent thermal and combustion performance of Al/MoO3/Kp nanothermite is attributed to the melt and decomposition of Kp into O2 in the third stage. This study provides new ideas and guidance for the design of high-performance nanothermites.

Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on noncontrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS) ≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from a prospectively maintained database. The primary outcome was favorable functional outcome [modified Rankin Scale score (mRS), 0-3] at 90 days. Safety outcomes included 48 h symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT+SMT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only [adjusted risk ratio (RR), 1.86; 95% CI: 1.43-2.42, P <0.001; adjusted risk difference (RD), 13.77; 95% CI: 7.40-20.15, P <0.001]. The proportion of sICH was significantly higher in patients undergoing EVT (13.3 vs. 2.4%; adjusted RR, 5.17; 95% CI: 2.17-12.32, P <0.001; adjusted RD, 10.10; 95% CI: 6.12-14.09, P <0.001). No significant difference of mortality between the groups was observed (41.8 vs. 49.0%; adjusted RR, 0.91; 95% CI: 0.77-1.07, P =0.24; adjusted RD, -5.91; 95% CI: -12.91-1.09, P =0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real-world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were relatively higher in the EVT+SMT group.

Therapeutic efficacy of tranexamic acid on traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) demonstrates therapeutic efficacy in the management of traumatic brain injury (TBI). The objective of this systematic review and meta-analysis was to evaluate the safety and effectiveness of TXA in patients with TBI. METHODS: The databases, namely PubMed, Embase, Web of Science, and Cochrane Library databases, were systematically searched to retrieve randomized controlled trials (RCTs) investigating the efficacy of TXA for TBI from January 2000 to November 2023. RESULTS: The present meta-analysis incorporates ten RCTs. Compared to the placebo group, administration of TXA in patients with TBI resulted in a significant reduction in mortality (P = 0.05), hemorrhage growth (P = 0.03), and volume of hemorrhage growth (P = 0.003). However, no significant impact was observed on neurosurgery outcomes (P = 0.25), seizure occurrence (P = 0.78), or pulmonary embolism incidence (P = 0.52). CONCLUSION: The administration of TXA is significantly associated with reduced mortality and hemorrhage growth in patients suffering from TBI, while the need of neurosurgery, seizures, and incidence of pulmonary embolism remains comparable to that observed with placebo.

Genome assembly and multi-omic analyses reveal the mechanisms underlying flower color formation in Torenia fournieri.

Torenia fournieri Lind. is an ornamental plant that is popular for its numerous flowers and variety of colors. However, its genomic evolutionary history and the genetic and metabolic bases of flower color formation remain poorly understood. Here, we report the first T. fournieri reference genome, which was resolved to the chromosome scale and was 164.4 Mb in size. Phylogenetic analyses clarified relationships with other plant species, and a comparative genomic analysis indicated that the shared ancestor of T. fournieri and Antirrhinum majus underwent a whole genome duplication event. Joint transcriptomic and metabolomic analyses identified many metabolites related to pelargonidin, peonidin, and naringenin production in rose (TfR)-colored flowers. Samples with blue (TfB) and deep blue (TfD) colors contained numerous derivatives of petunidin, cyanidin, quercetin, and malvidin; differences in the abundances of these metabolites and expression levels of the associated genes were hypothesized to be responsible for variety-specific differences in flower color. Furthermore, the genes encoding flavonoid 3-hydroxylase, anthocyanin synthase, and anthocyanin reductase were differentially expressed between flowers of different colors. Overall, we successfully identified key genes and metabolites involved in T. fournieri flower color formation. The data provided by the chromosome-scale genome assembly establish a basis for understanding the differentiation of this species and will facilitate future genetic studies and genomic-assisted breeding.

Structure-Guided Discovery of Potent and Selective CLK2 Inhibitors for the Treatment of Knee Osteoarthritis.

Osteoarthritis is the most common joint disorder. However, there are no disease-modifying drugs approved for OA treatment. CDC2-like kinase 2 (CLK2) could modulate Wnt signaling via alternative splicing of Wnt target genes and further affect bone differentiation, chondrocyte function, and inflammation, making CLK2 an attractive target for OA therapy. In this study, we designed and synthesized a series of highly potent CLK2 inhibitors based on Indazole 1. Among them, compound LQ23 showed more elevated inhibitory activity against CLK2 than the lead compound (IC50, 1.4 nM) with high CLK2/CLK3 selectivity (>70-fold). Furthermore, LQ23 showed outstanding antiosteoarthritis effects in vitro and in vivo, with the roles specific in decreased inflammatory cytokines, downregulated cartilage degradative enzymes, and increased joint cartilage via suppressing CLK2/Wnt signaling pathway. Overall, these data support LQ23 as a potential candidate for intra-articular knee OA therapy, leveraging its unique mechanism of action for targeted treatment.

The CK1ε/SIAH1 axis regulates AXIN1 stability in colorectal cancer cells.

Casein kinase 1ε (CK1ε) and axis inhibitor 1 (AXIN1) are crucial components of the ß-catenin destruction complex in canonical Wnt signaling. CK1ε has been shown to interact with AXIN1, but its physiological function and role in tumorigenesis remain unknown. In this study, we found that CK1δ/ε inhibitors significantly enhanced AXIN1 protein level in colorectal cancer (CRC) cells through targeting CK1ε. Mechanistically, CK1ε promoted AXIN1 degradation by the ubiquitin-proteasome pathway by promoting the interaction of E3 ubiquitin-protein ligase SIAH1 with AXIN1. Genetic or pharmacological inhibition of CK1ε and knockdown of SIAH1 downregulated the expression of Wnt/ß-catenin-dependent genes, suppressed the viability of CRC cells, and restrained tumorigenesis and progression of CRC in vitro and in vivo. In summary, our results demonstrate that CK1ε exerted its oncogenic role in CRC occurrence and progression by regulating the stability of AXIN1. These findings reveal a novel mechanism by which CK1ε regulates the Wnt/ß-catenin signaling pathway and highlight the therapeutic potential of targeting the CK1ε/SIAH1 axis in CRC.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Efficient degradation of polystyrene microplastic pollutants in soil by dielectric barrier discharge plasma.

In this study, the atmospheric dielectric barrier discharge (DBD) plasma was proposed for the degradation of polystyrene microplastics (PS-MPs) for the first time, due to its ability to generate reactive oxygen species (ROS). The local temperature in plasma was found to play a crucial role, as it enhanced the degradation reaction induced by ROS when it exceeded the melting temperature of PS-MPs. Factors including applied voltage, air flow rate, and PS-MPs concentration were investigated, and the degradation products were analyzed. High plasma energy and adequate supply of ROS were pivotal in promoting degradation. At 20.1 kV, the degradation efficiency of PS-MPs reached 98.7% after 60 min treatment, with gases (mainly COx, accounting for 96.4%) as the main degradation products. At a concentration of 1 wt%, the PS-MPs exhibited a remarkable conversion rate of 90.6% to COx, showcasing the degradation performance and oxidation degree of this technology. Finally, the degradation mechanism of PS-MPs combined with the detection results of ROS was suggested. This work demonstrates that DBD plasma is a promising strategy for PS-MPs degradation, with high energy efficiency (8.80 mg/kJ) and degradation performance (98.7% within 1 h), providing direct evidence for the rapid and comprehensive treatment of MP pollutants.

Integrated physiological, metabolomic, and transcriptomic analyses elucidate the regulation mechanisms of lignin synthesis under osmotic stress in alfalfa leaf (Medicago sativa L.).

Alfalfa, an essential forage crop known for its high yield, nutritional value, and strong adaptability, has been widely cultivated worldwide. The yield and quality of alfalfa are frequently jeopardized due to environmental degradation. Lignin, a constituent of the cell wall, enhances plant resistance to abiotic stress, which often causes osmotic stress in plant cells. However, how lignin responds to osmotic stress in leaves remains unclear. This study explored the effects of osmotic stress on lignin accumulation and the contents of intermediate metabolites involved in lignin synthesis in alfalfa leaves. Osmotic stress caused an increase in lignin accumulation and the alteration of core enzyme activities and gene expression in the phenylpropanoid pathway. We identified five hub genes (CSE, CCR, CADa, CADb, and POD) and thirty edge genes (including WRKYs, MYBs, and UBPs) by integrating transcriptome and metabolome analyses. In addition, ABA and ethylene signaling induced by osmotic stress regulated lignin biosynthesis in a contradictory way. These findings contribute to a new theoretical foundation for the breeding of high-quality and resistant alfalfa varieties.

Genome-wide identification and expression analysis of the glycosyl hydrolase family 1 genes in Medicago sativa revealed their potential roles in response to multiple abiotic stresses.

Glycoside hydrolase family 1 (GH1) ß-glucosidases (BGLUs), are encoded by a large number of genes, which participate in the development and stress response of plants, particularly under biotic and abiotic stresses through the activation of phytohormones. However, there are few studies systematically analyzing stress or hormone-responsive BGLU genes in alfalfa. In this study, a total of 179 BGLU genes of the glycoside hydrolase family 1 were identified in the genome of alfalfa, and then were classified into five distinct clusters. Sequence alignments revealed several conserved and unique motifs among these MsBGLU proteins. Many cis-acting elements related to abiotic stresses and phytohormones were identified in the promoter of some MsBGLUs. Moreover, RNA-seq and RT-qPCR analyses showed that these MsBGLU genes exhibited distinct expression patterns in response to different abiotic stress and hormonal treatments. In summary, this study suggests that MsBGLU genes play crucial roles in response to various abiotic stresses and hormonal responses, and provides candidate genes for stress tolerance breeding in alfalfa.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).