Acute ischemic stroke with or without asymptomatic intracranial hemorrhage after endovascular treatment: a propensity-score matching study.

BACKGROUND: The long-term follow-up of asymptomatic intracranial hemorrhage (aICH) in patients with acute ischemic stroke after endovascular treatment (EVT) remains controversial.ObjectiveTo evaluate the potential effect of aICH in a real-world practice setting using a matched prospective database. METHODS: This observational cohort study enrolled patients between January 2015 and December 2022 in a prospective database. Eligible patients with occlusions in the anterior circulation were given endovascular treatment and achieved successful reperfusion. The primary outcome was functional independence (modified Rankin Scale (mRS) score 0-2). Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: 732 patients, 516 without any ICH and 216 with aICH, were included. 418 and 348 patients were identified after matching in the aICH substudy and hemorrhagic infarction type aICH substudy, respectively. In the postmatched population, patients with aICH had worse functional outcomes (mRS score 0-2) at 90 days than patients without any ICH (37.8% vs 55.5%: P<0.001). Worse functional outcomes were seen in patients with aICH who were older (OR=5.59 (95% CI 2.91 to 10.74)), had higher baseline National Institutes of Health Stroke Scale score (OR=6.80 (95% CI 3.72 to 12.43)), lower baseline Alberta Stroke Program Early CT Score (OR=2.08 (95% CI 1.23 to 3.51)), and who received general anesthesia (OR=3.37 (95% CI 1.92 to 5.90)). CONCLUSIONS: This matched-control study largely confirmed that asymptomatic ICH after EVT is associated with worse functional outcomes, and the harmful effect is more significant in older patients and those with severe baseline clinical and radiological features.

Single and combined effect of polyethylene microplastics (virgin and naturally aged) and cadmium on pakchoi (Brassica rapa subsp. chinensis) under different growth stages.

To protect agro-systems and food security, study on the effect of microplastics and heavy metals on edible plants is of great significance. Existing studies mostly used virgin microplastics to evaluate their effects on plants, effects of naturally aged microplastics and their combined effects with heavy metals are rarely explored. In this study, single and combined effect of polyethylene microplastics (PE, both virgin and naturally aged) and cadmium (Cd) on pakchoi under seedling and mature stages were analyzed from perspectives of growth inhibition, oxidative damage, nutrition content and soil enzyme activities. Results showed that inhibiting effects of naturally aged PE (PEa) on the growth of pakchoi were stronger than virgin PE (PEv), whereas co-contamination of PEa and Cd was less toxic than that of PEv and Cd. The co-contamination of PE and Cd could inhibit pakchoi dry biomass by over 85 %. Both single and combined contamination of PE and Cd promoted soil fluorescein diacetate hydrolase (FDA) activities, which were 1.11 to 2.04 times of that in control group. Soluble sugar contents under co-contamination of PEa and Cd were 14 % to 22 % higher than those in control group. PEa and PEv showed different effects on oxidative damage of pakchoi. Compared with PEv, catalase (CAT) activities were more sensitive with PEa, whereas PEa had lower effect on superoxide dismutase (SOD) activities. The response of pakchoi to PE and Cd changed with growth stage. Chlorophyll contents in pakchoi under seedling stage were generally higher than those under mature stage. For Cd contaminated soils, PE benefited pakchoi growth under seedling stage, i.e. antagonistic effect between Cd and PE but hindered their growth under mature stage, i.e. synergistic effect. The results unraveled here emphasized PE, especially PEa, could trigger negative effects on agro-systems, whereas PE could be beneficial for heavy metal contaminated agro-systems under specific situations.

A cuproptosis-based nanomedicine suppresses triple negative breast cancers by regulating tumor microenvironment and eliminating cancer stem cells.

Cuproptosis is a new kind of cell death that depends on delivering copper ions into mitochondria to trigger the aggradation of tricarboxylic acid (TCA) cycle proteins and has been observed in various cancer cells. However, whether cuproptosis occurs in cancer stem cells (CSCs) is unexplored thus far, and CSCs often reside in a hypoxic tumor microenvironment (TME) of triple negative breast cancers (TNBC), which suppresses the expression of the cuproptosis protein FDX1, thereby diminishing anticancer efficacy of cuproptosis. Herein, a ROS-responsive active targeting cuproptosis-based nanomedicine CuET@PHF is developed by stabilizing copper ionophores CuET nanocrystals with polydopamine and hydroxyethyl starch to eradicate CSCs. By taking advantage of the photothermal effects of CuET@PHF, tumor hypoxia is overcome via tumor mechanics normalization, thereby leading to enhanced cuproptosis and immunogenic cell death in 4T1 CSCs. As a result, the integration of CuET@PHF and mild photothermal therapy not only significantly suppresses tumor growth but also effectively inhibits tumor recurrence and distant metastasis by eliminating CSCs and augmenting antitumor immune responses. This study presents the first evidence of cuproptosis in CSCs, reveals that disrupting hypoxia augments cuproptosis cancer therapy, and establishes a paradigm for potent cancer therapy by simultaneously eliminating CSCs and boosting antitumor immunity.

The difference between tire wear particles and polyethylene microplastics in stormwater filtration systems: Perspectives from aging process, conventional pollutants removal and microbial communities.

Tire wear particles (TWPs) in stormwater runoff have been widely detected and were generally classified into microplastics (MPs). TWPs and conventional MPs can be intercepted and accumulated in stormwater filtration systems, but their impacts on filtration, adsorption and microbial degradation processes of conventional pollutants (organic matters, nitrate and ammonium) have not been clarified. TWPs are different from MPs in surface feature, chemical components, adsorption ability and leaching of additives, which might lead to their different impacts on conventional pollutants removal. In this study, five different levels of aged polyethylene MPs (PEMPs) and aged TWPs contamination in stormwater filtration systems were simulated using thirty-three filtration columns. Results showed that ultraviolet aging treatment was less influential for the aging of TWPs than that of PEMPs, the specific surface area of aged PEMPs (1.603 m2/g) was over two times of unaged TWPs (0.728 m2/g) in the same size. Aged PEMPs and aged TWPs had different impacts on conventional pollutants removal performance and microbial communities, and the difference might be enlarged with exposure duration. The intensified aged PEMPs contamination generally promoted conventional pollutants removal, whereas aged TWPs showed an opposite trend. Mild contamination (0.01% and 0.1%, wt%) of aged PEMP/TWPs was beneficial to the richness and diversity of microbial communities, whereas higher contamination of aged PEMPs/TWPs was harmful. Aged PEMPs and TWPs had different impact on microbial community structure. Overall, the study found that TWPs were more detrimental than PEMPs in filtration systems. The research underscores the need for more comprehensive investigation into the occurrence, effects and management strategies of TWPs, as well as the importance of distinguishing between TWPs and MPs in future studies.

Hydroxyethyl starch-based self-reinforced nanomedicine inhibits both glutathione and thioredoxin antioxidant pathways to boost reactive oxygen species-powered immunotherapy.

The adaptive antioxidant systems of tumor cells, predominantly glutathione (GSH) and thioredoxin (TRX) networks, severely impair photodynamic therapy (PDT) potency and anti-tumor immune responses. Here, a multistage redox homeostasis nanodisruptor (Phy@HES-IR), integrated by hydroxyethyl starch (HES)-new indocyanine green (IR820) conjugates with physcion (Phy), an inhibitor of the pentose phosphate pathway (PPP), is rationally designed to achieve PDT primed cancer immunotherapy. In this nanodisruptor, Phy effectively depletes intracellular GSH of tumor cells by inhibiting 6-phosphogluconate dehydrogenase (6PGD) activity. Concurrently, it is observed for the first time that the modified IR820-NH2 molecule not only exerts PDT action but also interferes with TRX antioxidant pathway by inhibiting thioredoxin oxidase (TRXR) activity. The simultaneous weakening of two major antioxidant pathways of tumor cells is favorable to maximize the PDT efficacy induced by HES-IR conjugates. By virtue of the excellent protecting ability of the plasma expander HES, Phy@HES-IR can remain stable in the blood circulation and efficiently enrich in the tumor region. Consequently, PDT and metabolic modulation synergistically induced immunogenic cell death, which not only suppressed primary tumors but also stimulated potent anti-tumor immunity to inhibit the growth of distant tumors in 4T1 tumor-bearing mice.

A review of volatile fatty acids production from organic wastes: Intensification techniques and separation methods.

High value-added products from organic waste fermentation have garnered increasing concern in modern society. VFAs are short-chain fatty acids, produced as intermediate products during the anaerobic fermentation of organic matter. VFAs can serve as an essential organic carbon source to produce substitutable fuels, microbial fats and oils, and synthetic biodegradable plastics et al. Extracting VFAs from the fermentation broths is a challenging task as the composition of suspensions is rather complex. In this paper, a comprehensive review of methods for VFAs production, extraction and separation are provided. Firstly, the methods to enhance VFAs production and significant operating parameters are briefly reviewed. Secondly, the evaluation and detailed discussion of various VFAs extraction and separation technologies, including membrane separation, complex extraction, and adsorption methods, are presented, highlighting their specific advantages and limitations. Finally, the challenges encountered by different separation technologies and novel approaches to enhance process performance are highlighted, providing theoretical guidance for recycling VFAs from organic wastes efficiently.

Softness-Aided Mild Hyperthermia Boosts Stiff Nanomedicine by Regulating Tumor Mechanics.

Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer-associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild-hyperthermia photothermal therapy (mild-PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)-loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild-PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)-loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness-mediated mild-PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism.

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

TGF-ß downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

Effect of Clot Burden Score on Safety and Efficacy of Intravenous Alteplase Prior to Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Analysis of a Randomized Phase 3 Trial.

BACKGROUND AND PURPOSE: Whether thrombus burden in acute ischemic stroke modify the effect of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remains uncertain. We aim to investigate the treatment effect of stratified clot burden score (CBS) on the efficacy and safety of direct versus bridging MT. MATERIALS AND METHODS: This is an exploratory subgroup analysis of a randomized trial evaluating the effect of CBS on clinical outcome in the DIRECT-MT trial. CBS was divided into 3 groups (0-3, 4-6, and 7-10) based on preoperative CTA, where higher scores indicated a lower clot burden. We report the adjusted common odds ratio for a shift toward better outcomes on the mRS after thrombectomy alone compared with combination treatment by stratified CBS groups. RESULTS: No modification effect of mRS distribution was observed by CBS subgroups (CBS 0-3: adjusted common ratio odds 1.519 [95% CI, 0.928-2.486]; 4-6: 0.924 [0.635-1.345]; 7-10: 1.040 [0.481-2.247]). Patients with CBS 4-6 had a higher rate of early reperfusion (adjusted OR (aOR), 0.3 [95% CI, 0.1-0.9]), final reperfusion (aOR 0.5 [95% CI, 0.3-0.9]), and fewer thrombectomy attempts (aOR 0.4 [95% CI, 0.1-0.7]). Patients with CBS 7-10 had a higher rate of asymptomatic intracranial hemorrhage (14.9% versus 36.8%, P = .0197) for bridging MT. No significant difference was observed in other safety outcomes by trichotomized CBS. CONCLUSIONS: The subgroup analysis of DIRECT-MT suggested that thrombus burden did not alter the treatment effect of IVT before MT on functional outcomes in CBS subgroups.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.

A review of lipid accumulation by oleaginous yeasts: Culture mode.

Microbial lipids have attracted considerable interest owing to their favorable environmental sustainability benefits. In laboratory-scale studies, the factors impacting lipid production in oleaginous yeasts, including culture conditions, nutrients, and low-cost substrates, have been extensively studied. However, there were several different modes of microbial lipid cultivation (batch culture, fed-batch culture, continuous culture, and other novel culture modes), making it difficult to comprehensively analyze impacting factors under different cultivation modes on a laboratory scale. And only few cases of microbial lipid production have been conducted at the pilot scale, which requires more technological reliability assessments and environmental benefit evaluations. Thus, this study summarized the different culture modes and cases of scale-up processes, highlighting the role of the nutrient element ratio in regulating culture mode selection and lipid accumulation. The cost distribution and environmental benefits of microbial lipid production by oleaginous yeasts were also investigated. Our results suggested that the continuous culture mode was recommended for the scale-up process because of its stable lipid accumulation. More importantly, exploring the continuous culture mode integrated with other efficient culture modes remained to be further investigated. In research on scale-up processes, low-cost substrate (organic waste) application and optimization of reactor operational parameters were key to increasing environmental benefits and reducing costs.

Ferroptosis mediated by TNFSF9 interferes in acute ischaemic stroke reperfusion injury with the progression of acute ischaemic stroke.

In this study, we investigated the potential involvement of TNFSF9 in reperfusion injury associated with ferroptosis in acute ischaemic stroke patients, mouse models and BV2 microglia. We first examined TNFSF9 changes in peripheral blood from stroke patients with successful reperfusion, and constructed oxygen-glucose deprivation-reperfusion (OGD-R) on BV2 microglia, oxygen-glucose deprivation for 6 h followed by reoxygenation and re-glucose for 24 h, and appropriate over-expression or knockdown of TNFSF9 manipulation on BV2 cells and found that in the case of BV2 cells encountering OGD-R over-expression of TNFSF9 resulted in increased BV2 apoptosis. Still, the knockdown of TNFSF9 ameliorated apoptosis and ferroptosis. In an in vivo experiment, we constructed TNFSF9 over-expression or knockout mice by intracerebral injection of TNFSF9-OE or sh-TNFSF9 adenovirus. We performed the middle cerebral artery occlusion (MCAO) model on day four, 24 h after ligation of the proximal artery, for half an hour to recanalize. As luck would have it, over-expression of TNFSF9 resulted in increased brain infarct volumes, neurological function scores and abnormalities in TNFSF9-related TRAF1 and ferroptosis-related pathways, but knockdown of TNFSF9 improved brain infarcts in mice as well as reversing TNFSF9-related signalling pathways. In conclusion, our data provide the first evidence that TNFSF9 triggers microglia activation by activating the ferroptosis signalling pathway following ischaemic stroke, leading to brain injury and neurological deficits.

Glutaminolysis inhibition boosts photodynamic therapy to eliminate cancer stem cells.

High reactive oxygen species (ROS) levels provide a therapeutic opportunity to eradicate cancer stem cells (CSCs), a population of cells responsible for tumorigenesis, progression, metastasis, and recurrence. However, enhanced antioxidant systems in this population of cells attenuate ROS-inducing therapies. Here, we developed a nanoparticle-assisted combination therapy to eliminate CSCs by employing photodynamic therapy (PDT) to yield ROS while disrupting ROS defense with glutaminolysis inhibition. Specifically, we leveraged an oleic acid-hemicyanine conjugate (CyOA) as photosensitizer, a new entity molecule HYL001 as glutaminolysis inhibitor, and a biocompatible folic acid-hydroxyethyl starch conjugate (FA-HES) as amphiphilic surfactant to construct cellular and mitochondrial hierarchical targeting nanomedicine (COHF NPs). COHF NPs inhibited glutaminolysis to reduce intracellular ROS scavengers, including glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH), and to blunt oxidative phosphorylation (OXPHOS) for oxygen-conserved PDT. Compared to COLF NPs without glutaminolysis inhibitor, COHF NPs exhibited higher phototoxicity to breast cancer stem cells (BCSCs) both in vitro and in vivo. More importantly, we corroborated that marketed glutaminolysis inhibitors, such as CB839 and V9302, augment the clinically used photosensitizer (Hiporfin) for BCSCs elimination. This study develops a potent CSCs targeting strategy by combining glutaminolysis inhibition with PDT and provides significant implications for cancer therapy.

What is the role of nitrate/nitrite in trace organic contaminants degradation and transformation during UV-based advanced oxidation processes?

The effectiveness of UV-based advanced oxidation processes (UV-AOPs) in degrading trace organic contaminants (TrOCs) can be significantly influenced by the ubiquitous presence of nitrate (NO3-) and nitrite (NO2-) in water and wastewater. Indeed, NO3-/NO2- can play multiple roles of NO3-/NO2- in UV-AOPs, leading to complexities and conflicting results observed in existing research. They can inhibit the degradation of TrOCs by scavenging reactive species and/or competitively absorbing UV light. Conversely, they can also enhance the elimination of TrOCs by generating additional •OH and reactive nitrogen species (RNS). Furthermore, the presence of NO3-/NO2- during UV-AOP treatment can affect the transformation pathways of TrOCs, potentially resulting in the nitration/nitrosation of TrOCs. The resulting nitro(so)-products are generally more toxic than the parent TrOCs and may become precursors of nitrogenous disinfection byproducts (N-DBPs) upon chlorination. Particularly, since the impact of NO3-/NO2- in UV-AOPs is largely due to the generation of RNS from NO3-/NO2- including NO•, NO2•, and peroxynitrite (ONOO-/ONOOH), this review covers the generation, properties, and detection methods of these RNS. From kinetic, mechanistic, and toxicologic perspectives, future research needs are proposed to advance the understanding of how NO3-/NO2- can be exploited to improve the performance of UV-AOPs treating TrOCs. This critical review provides a comprehensive framework outlining the multifaceted impact of NO3-/NO2- in UV-AOPs, contributing insights for basic research and practical applications of UV-AOPs containing NO3-/NO2-.

GRIN2A mutation is a novel indicator of stratifying beneficiaries of immune checkpoint inhibitors in multiple cancers.

Glutamate-NMDAR receptors (GRINs) have been reported to influence cancer immunogenicity; however, the relationship between GRIN alterations and the response to immune checkpoint inhibitors (ICIs) has not been determined. This study combined clinical characteristics and mutational profiles from multiple cohorts to form a discovery cohort (n = 901). The aim of this study was to investigate the correlation between the mutation status of the GRIN gene and the response to ICI therapy. Additionally, an independent ICI-treated cohort from the Memorial Sloan Kettering Cancer Center (MSKCC, N = 1513) was used for validation. Furthermore, this study explored the associations between GRIN2A mutations and intrinsic and extrinsic immunity using multiomics analysis. In the discovery cohort, patients with GRIN2A-MUTs had improved clinical outcomes, as indicated by a higher objective response rate (ORR: 36.8% vs 25.8%, P = 0.020), durable clinical benefit (DCB: 55.2% vs 38.7%, P = 0.005), prolonged progression-free survival (PFS: HR = 0.65; 95% CI 0.49 to 0.87; P = 0.003), and increased overall survival (OS: HR = 0.67; 95% CI 0.50 to 0.89; P = 0.006). Similar results were observed in the validation cohort, in which GRIN2A-MUT patients exhibited a significant improvement in overall survival (HR = 0.66; 95% CI = 0.49 to 0.88; P = 0.005; adjusted P = 0.045). Moreover, patients with GRIN2A-MUTs exhibited an increase in tumor mutational burden, high expression of costimulatory molecules, increased activity of antigen-processing machinery, and infiltration of various immune cells. Additionally, gene sets associated with cell cycle regulation and the interferon response were enriched in GRIN2A-mutated tumors. In conclusion, GRIN2A mutation is a novel biomarker associated with a favorable response to ICIs in multiple cancers.

Gekko Coil System for Intracranial Aneurysms Treatment in China (GREAT-China): A Prospective Randomized Controlled Open-Label Noninferiority Trial.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of the Gekko coil system in treating intracranial aneurysms (IAs) in clinical practice. METHODS: A prospective multicenter randomized open-label parallel positive control noninferiority trial was conducted by 11 centers in China. Patients with a target IA were randomized 1:1 to coiling with either Gekko or Axium coils. The primary outcome was successful aneurysm occlusion at 6 months postoperative follow-up, whereas the secondary outcomes included the successful occlusion aneurysm rate in the immediate postoperative period, recanalization rate at the 6 months follow-up, and technical success and security. RESULTS: Between May 2018 and September 2020, 256 patients were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 96.08% for the Gekko coil group compared with 96.12% in the Axium coil group, with a difference of -0.04% (P = 0.877). The successful immediate aneurysm occlusion rates were 86.00% and 77.45% in the Gekko coil group and the Axium coil group, respectively, showing no significant difference between the 2 groups (P = 0.116), whereas the recanalization rates during the 6 months follow-up were 2.02% and 1.96% in the Gekko and Axium coil groups, respectively, which was not statistically significant (P = 1.000). CONCLUSIONS: This trial showed that the Gekko coil system was noninferior to the Axium coil system in terms of efficacy and safety for IA embolization. In clinical practice, the Gekko coil system can be considered safe and effective for treating patients with IA.

What makes residents participate in the rural toilet revolution?

•Motivation of Chinese rural residents to participate in RTR identified•Motivational model of Chinese rural resident participating in RTR is constructed•Model includes intrinsic and extrinsic factors, and impacts of RTR policy•RTR policy may influence rural residents' final decision to participate RTR.

Quantum-enhanced diamond molecular tension microscopy for quantifying cellular forces.

The constant interplay and information exchange between cells and the microenvironment are essential to their survival and ability to execute biological functions. To date, a few leading technologies such as traction force microscopy, optical/magnetic tweezers, and molecular tension-based fluorescence microscopy are broadly used in measuring cellular forces. However, the considerable limitations, regarding the sensitivity and ambiguities in data interpretation, are hindering our thorough understanding of mechanobiology. Here, we propose an innovative approach, namely, quantum-enhanced diamond molecular tension microscopy (QDMTM), to precisely quantify the integrin-based cell adhesive forces. Specifically, we construct a force-sensing platform by conjugating the magnetic nanotags labeled, force-responsive polymer to the surface of a diamond membrane containing nitrogen-vacancy centers. Notably, the cellular forces will be converted into detectable magnetic variations in QDMTM. After careful validation, we achieved the quantitative cellular force mapping by correlating measurement with the established theoretical model. We anticipate our method can be routinely used in studies like cell-cell or cell-material interactions and mechanotransduction.

Low-temperature methanation of fermentation gas with Ni-based catalysts in a multicomponent system.

A large amount of greenhouse gases, such as carbon dioxide and methane, are released during the production process of bioethanol and biogas. Converting CO2 into methane is a promising way of capturing CO2 and generating high-value gas. At present, CO2 methanation technology is still in the early stage. It requires high temperature (300-400 â„ƒ) and pressure (> 1 MPa), leading to high cost and energy consumption. In this study, a new catalyst, Ni-Fe/Al-Ti, was developed. Compared with the activity of the common Ni/Al2O3 catalyst, that of the new catalyst was increased by 1/3, and its activation temperature was reduced by 100℃. The selectivity of methane was increased to 99%. In the experiment using simulated fermentation gas, the catalyst showed good catalytic activity and durability at a low temperature and atmospheric pressure. Based on the characterization of catalysts and the study of reaction mechanisms, this article innovatively proposed a Ni-Fe/Al-Ti quaternary catalytic system. Catalytic process was realized through the synergism of Al-Ti composite support and Ni-Fe promotion. The oxygen vacancies on the surface of the composite carrier and the higher activity metals and alloys promoted by Fe accelerate the capture and reduction of CO2. Compared with the existing catalysts, the new Ni-Fe/Al-Ti catalyst can significantly improve the methanation efficiency and has great practical application potential.