Twinning Engineering of Platinum/Iridium Nanonets as Turing-Type Catalysts for Efficient Water Splitting.

The twin boundary, a common lattice plane of mirror-symmetric crystals, may have high reactivity due to special atomic coordination. However, twinning platinum and iridium nanocatalysts are grand challenges due to the high stacking fault energies that are nearly 1 order of magnitude larger than those of easy-twinning gold and silver. Here, we demonstrate that Turing structuring, realized by selective etching of superthin metal film, provides 14.3 and 18.9 times increases in twin-boundary densities for platinum and iridium nanonets, comparable to the highly twinned silver nanocatalysts. The Turing configurations with abundant low-coordination atoms contribute to the formation of nanotwins and create a large active surface area. Theoretical calculations reveal that the specific atom arrangement on the twin boundary changes the electronic structure and reduces the energy barrier of water dissociation. The optimal Turing-type platinum nanonets demonstrated excellent hydrogen-evolution-reaction performance with a 25.6 mV overpotential at 10.0 mA·cm-2 and a 14.8-fold increase in mass activity. And the bifunctional Turing iridium catalysts integrated in the water electrolyzer had a mass activity 23.0 times that of commercial iridium catalysts. This work opens a new avenue for nanocrystal twinning as a facile paradigm for designing high-performance nanocatalysts.

Low Pneumoperitoneum Pressure Reduces Gas Embolism During Laparoscopic Liver Resection: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of low and standard pneumoperitoneal pressure (PP) on the occurrence of gas embolism during laparoscopic liver resection (LLR). BACKGROUND: LLR has an increased risk of gas embolism. Although animal studies have shown that low PP reduces the occurrence of gas embolism, clinical evidence is lacking. METHODS: This parallel, dual-arm, double-blind, randomized controlled trial included 141 patients undergoing elective LLR. Patients were randomized into standard ("S," 15 mm Hg; n = 70) or low ("L," 10 mm Hg; n = 71) PP groups. Severe gas embolism (≥ grade 3, based on the Schmandra microbubble method) was detected using transesophageal echocardiography and recorded as the primary outcome. Intraoperative vital signs and postoperative recovery profiles were also evaluated. RESULTS: Fewer severe gas embolism cases (n = 29, 40.8% vs n = 47, 67.1%, P = 0.003), fewer abrupt decreases in end-tidal carbon dioxide partial pressure, shorter severe gas embolism duration, less peripheral oxygen saturation reduction, and fewer increases in heart rate and lactate during gas embolization episodes was found in group L than in group S. Moreover, a higher arterial partial pressure of oxygen and peripheral oxygen saturation were observed, and fewer fluids and vasoactive drugs were administered in group L than in group S. In both groups, the distensibility index of the inferior vena cava negatively correlated with central venous pressure throughout LLR, and a comparable quality of recovery was observed. CONCLUSIONS: Low PP reduced the incidence and duration of severe gas embolism and achieved steadier hemodynamics and vital signs during LLR. Therefore, a low PP strategy can be considered a valuable choice for the future LLR.

Breaking the Solubility Limit of LiNO3 in Carbonate Electrolyte Assisted by BF3 to Construct a Stable SEI Film for Dendrite-Free Lithium Metal Batteries.

Lithium (Li) metal is regarded as a potential candidate for the next generation of lithium secondary batteries, but it has poor cycling stability with the broadly used carbonate-based electrolytes due to the uncontrollable dendritic growth and low Coulombic efficiency (CE). LiNO3 is an effective additive and its limited solubility (<800 ppm) in carbonate-based electrolytes is still a challenge, as reported. Herein, using BF3 (Lewis acid) is proposed to enhance the solubility of LiNO3 in carbonate-based electrolytes. The dissolved NO3 - can be involved in the first solvation shell of Li+, reducing the coordination number of PF6 - and EC (ethylene carbonate). In addition, the NO3 - is proved to be preferentially reduced on Li metal by differential electrochemical mass spectrometry so that the decomposition of PF6 - and EC is suppressed. Therefore, a SEI layer containing Li3N can be obtained, which exhibits high lithium-ion conductivity, achieving even and dense Li deposits. Consequently, the CE of Li||Cu cell with BF3/LiNO3 can be increased to 98.07%. Moreover, the capacity retention of Li||LiFePO4 with a low N/P ratio (3:1) is as high as 90% after 300 cycles (≈1500 h). This work paved a new way for incorporating LiNO3 into carbonate-based electrolytes and high-performance lithium metal batteries.

Development of an 18F-labeled azobenzothiazole tracer for α-synuclein aggregates in the brain.

Nuclear imaging of aggregated α-synuclein pathology is an urgent clinical need for Parkinson's disease, yet promising tracers for brain α-synuclein aggregates are still rare. In this work, a class of compact benzothiazole derivatives was synthesized and evaluated for α-synuclein aggregates. Among them, azobenzothiazoles exhibited specific and selective detection of α-synuclein aggregates under physiological conditions. Fluoro-pegylated azobenzothiazole NN-F further demonstrated high-affinity binding to α-synuclein aggregates and efficient 18F-radiolabeling via nucleophilic displacement of a tosyl precursor. [18F]NN-F was stable in plasma in vitro and showed efficient brain uptake with little defluorination in vivo.

Exosomal lncRNA HEIH, an essential communicator for hepatocellular carcinoma cells and macrophage M2 polarization through the miR-98-5p/STAT3 axis.

Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-Related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

OBJECTIVES: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. STUDY DESIGN: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. RESULTS: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge (P=0.429) and 6 months after surgery (P=1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus (P=0.088), D dimer (P=0.412), catheter in situ days (P=0.281), and post-thrombotic syndrome (P=1.000), except for activated partial thromboplastin time (P=0.001). CONCLUSIONS: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Three-Dimensional Magnetic Resonance Imaging Fast Field Echo Resembling a Computed Tomography Using Restricted Echo-Spacing Sequence Is Equivalent to 3-Dimensional Computed Tomography in Quantifying Bone Loss and Measuring Shoulder Morphology in Patients With Shoulder Dislocation.

PURPOSE: To evaluate the equivalence of 3-dimensional (3D) magnetic resonance imaging (MRI) (FRACTURE [Fast field echo Resembling A CT Using Restricted Echo-spacing]) and 3D computed tomography (CT) in quantifying bone loss in patients with shoulder dislocation and measuring morphologic parameters of the shoulder. METHODS: From July 2022 to June 2023, patients with anterior shoulder dislocation who were aged 18 years or older and underwent both MRI and CT within 1 week were included in the study. The MRI protocol included an additional FRACTURE sequence. Three-dimensional reconstructions of MRI (FRACTURE) and CT were completed by 2 independent observers using Mimics software (version 21.0) through simple threshold-based segmentation. For bone defect cases, 2 independent observers evaluated glenoid defect, percentage of glenoid defect, glenoid track, Hill-Sachs interval, and on-track/off-track. For all cases, glenoid width, glenoid height, humeral head-fitting sphere radius, critical shoulder angle, glenoid version, vault depth, and post-processing time were assessed. The paired t test was used to assess the differences between 3D CT and 3D MRI (FRACTURE). Bland-Altman plots were constructed to evaluate the consistency between 3D CT and 3D MRI (FRACTURE). Interobserver and intraobserver agreement was evaluated with the interclass correlation coefficient. The paired χ2 test and Cohen κ statistic were used for binary variables (on-track/off-track). RESULTS: A total of 56 patients (16 with bipolar bone defect, 5 with only Hill-Sachs lesion, and 35 without bone defect) were ultimately enrolled in the study. The measurements of 21 bone defect cases showed no statistically significant differences between 3D CT and 3D MRI: glenoid defect, 4.05 ± 1.44 mm with 3D CT versus 4.16 ± 1.39 mm with 3D MRI (P = .208); percentage of glenoid defect, 16.21% ± 5.95% versus 16.61% ± 5.66% (P = .199); glenoid track, 18.02 ± 2.97 mm versus 18.08 ± 2.98 mm (P = .659); and Hill-Sachs interval, 14.29 ± 1.93 mm versus 14.35 ± 2.07 mm (P = .668). No significant difference was found between 3D CT and 3D MRI in the diagnosis of on-track/off-track (P > .999), and diagnostic agreement was perfect (κ = 1.00, P < .001). There were no statistically significant differences between the 2 examination methods in the measurements of all 56 cases, except that the post-processing time of 3D MRI was significantly longer than that of 3D CT: glenoid height, 34.56 ± 1.98 mm with 3D CT versus 34.67 ± 2.01 mm with 3D MRI (P = .139); glenoid width, 25.32 ± 1.48 mm versus 25.45 ± 1.47 mm (P = .113); humeral head-fitting sphere radius, 22.91 ± 1.70 mm versus 23.00 ± 1.76 mm (P = .211); critical shoulder angle, 33.49° ± 2.55° versus 33.57° ± 2.51° (P = .328); glenoid version, -3.25° ± 2.57° versus -3.18° ± 2.57° (P = .322); vault depth, 37.43 ± 1.68 mm versus 37.58 ± 1.75 mm (P = .164); and post-processing time, 89.66 ± 10.20 seconds versus 360.93 ± 26.76 seconds (P < .001). For all assessments, the Bland-Altman plots showed excellent consistency between the 2 examination methods, and the interclass correlation coefficients revealed excellent interobserver and intraobserver agreement. CONCLUSIONS: Three-dimensional MRI (FRACTURE) is equivalent to 3D CT in quantifying bone loss in patients with shoulder dislocation and measuring shoulder morphologic parameters. LEVEL OF EVIDENCE: Level II, development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding).

Standardizing norms for 1286 colored pictures in Cantonese.

This study established psycholinguistic norms in Cantonese for a set of 1286 colored pictures sourced from several picture databases, including 750 colored line drawings from MultiPic (Duñabeitia et al., 2018) and 536 photographs selected for McRae et al. (2005) concepts. The pictures underwent rigorous normalization processes. We provided picture characteristics including name and concept agreement, familiarity, visual complexity, and frequency of modal responses. Through correlational analyses, we observed strong interrelationships among these variables. We also compared the current Cantonese norming to other languages and demonstrated similarity and variations among different languages. Additionally, we embraced the multilingual diversity within the current sample, and found that higher Cantonese proficiency but lower non-native language proficiency were associated with better spoken picture naming. Last but not least, we validated the predictive power of normed variables calculated from typed responses to spoken picture naming, and the consistency between typed and spoken responses. The present norming provides a timely and valuable alternative for researchers in the field of psycholinguistics, especially those studying Cantonese production and lexical retrieval. All raw data, analysis scripts, and final norming results are available online as psycholinguistic norms for Cantonese in the following link at the Open Science Framework: https://osf.io/dz9j6/?view_only=a452d8a56c92430b9dedf21ac26b1bc1 .

[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

Compact Luminol Chemiluminophores for In Vivo Detection and Imaging of ß-Sheet Protein Aggregates.

Protein aggregation has been found in a wide range of neurodegenerative protein-misfolding diseases. The demand for in vivo technologies to identify protein aggregation is at the leading edge for the pathogenic study, diagnostic development, and therapeutic intervention of these devastating disorders. Herein, we report a series of luminol analogues to construct a facile chemiluminescence (CL)-based approach for in vivo detection and imaging of ß-sheet protein aggregates. The synthesized compounds exhibited a distinct chemiluminescent response with long emission wavelengths toward reactive oxygen species under physiological conditions and displayed signal amplification in the presence of ß-sheet protein aggregates, including α-synuclein, ß-amyloid, and tau. Among them, CyLumi-3 was further evaluated as a chemiluminescent probe in preclinical models. By intravenous administration into the model mice via the tail vein, in vivo CL imaging noninvasively detected the specific CL of the probe targeting the α-synuclein aggregates in the brains of living mice. Based on its structural characteristics, CyLumi-3 can readily interact with α-synuclein aggregates with significantly enhanced fluorescence and can identify α-synuclein aggregates in vivo via distinctive CL amplification, which could pave the way for a more comprehensive understanding of protein aggregation in preclinical studies and would provide new hints for developing small-molecule chemiluminophores for protein aggregates.

Uncovering the Redox Shuttle Degradation Mechanism of Ether Electrolytes in Sodium-Ion Batteries and its Inhibition Strategy.

Ether-based electrolytes exhibit excellent performance when applied in different anode materials of sodium ion batteries (SIBs), but their exploration on cathode material is deficient and the degradation mechanism is still undiscovered. Herein, various battery systems with different operation voltage ranges are designed to explore the electrochemical performance of ether electrolyte. It is found for the first time that the deterioration mechanism of ether electrolyte is closely related to the "redox shuttle" between cathode and low-potential anode. The "shuttle" is discovered to occur when the potential of anodes is below 0.57 V, and the gas products coming from "shuttle" intermediates are revealed by differential electrochemical mass spectrometry (DEMS). Moreover, effective inhibition strategies by protecting low-potential anodes are proposed and verified; ethylene carbonate (EC) is found to be very effective as an additive by forming an inorganics-rich solid electrolyte interphase (SEI) on low-potential anodes, thereby suppressing the deterioration of ether electrolytes. This work reveals the failure mechanism of ether-based electrolytes applied in SIBs and proposes effective strategies to suppress the "shuttle," which provides a valuable guidance for advancing the application of ether-based electrolytes in SIBs.

Antipsychotic drugs induce vascular defects in hematopoietic organs.

Antipsychotic agents are clinically utilized to treat schizophrenia and other mental disorders. These drugs induce neurological and metabolic side effects, but their influence on blood vessels remains largely unknown. Here, we show that haloperidol, one of the most frequently prescribed antipsychotic agents, induces vascular defects in bone marrow. Acute haloperidol treatment results in vascular dilation that is specific to hematopoietic organs. This vessel dilation is associated with disruption of hematopoiesis and hematopoietic stem/progenitor cells (HSPCs), both of which are reversible after haloperidol withdrawal. Mechanistically, haloperidol treatment blocked the secretion of vascular endothelial growth factor A (VEGF-A) from HSPCs. Genetic blockade of VEGF-A secretion from hematopoietic cells or inhibition of VEGFR2 in endothelial cells result in similar vessel dilation in bone marrow during regeneration after irradiation and transplantation. Conversely, VEGF-A gain of function rescues the bone marrow vascular defects induced by haloperidol treatment and irradiation. Our work reveals an unknown effect of antipsychotic agents on the vasculature and hematopoiesis with potential implications for drug application in clinic.

Lower-extremity fatigue fracture detection and grading based on deep learning models of radiographs.

OBJECTIVES: To identify the feasibility of deep learning-based diagnostic models for detecting and assessing lower-extremity fatigue fracture severity on plain radiographs. METHODS: This retrospective study enrolled 1151 X-ray images (tibiofibula/foot: 682/469) of fatigue fractures and 2842 X-ray images (tibiofibula/foot: 2000/842) without abnormal presentations from two clinical centers. After labeling the lesions, images in a center (tibiofibula/foot: 2539/1180) were allocated at 7:1:2 for model construction, and the remaining images from another center (tibiofibula/foot: 143/131) for external validation. A ResNet-50 and a triplet branch network were adopted to construct diagnostic models for detecting and grading. The performances of detection models were evaluated with sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), while grading models were evaluated with accuracy by confusion matrix. Visual estimations by radiologists were performed for comparisons with models. RESULTS: For the detection model on tibiofibula, a sensitivity of 95.4%/85.5%, a specificity of 80.1%/77.0%, and an AUC of 0.965/0.877 were achieved in the internal testing/external validation set. The detection model on foot reached a sensitivity of 96.4%/90.8%, a specificity of 76.0%/66.7%, and an AUC of 0.947/0.911. The detection models showed superior performance to the junior radiologist, comparable to the intermediate or senior radiologist. The overall accuracy of the diagnostic model was 78.5%/62.9% for tibiofibula and 74.7%/61.1% for foot in the internal testing/external validation set. CONCLUSIONS: The deep learning-based models could be applied to the radiological diagnosis of plain radiographs for assisting in the detection and grading of fatigue fractures on tibiofibula and foot. KEY POINTS: • Fatigue fractures on radiographs are relatively difficult to detect, and apt to be misdiagnosed. • Detection and grading models based on deep learning were constructed on a large cohort of radiographs with lower-extremity fatigue fractures. • The detection model with high sensitivity would help to reduce the misdiagnosis of lower-extremity fatigue fractures.

Mutant p53R211* ameliorates inflammatory arthritis in AIA rats via inhibition of TBK1-IRF3 innate immune response.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammation disease characterized by imbalance of immune homeostasis. p53 mutants are commonly described as the guardian of cancer cells by conferring them drug-resistance and immune evasion. Importantly, p53 mutations have also been identified in RA patients, and this prompts the investigation of its role in RA pathogenesis. METHODS: The cytotoxicity of disease-modifying anti-rheumatic drugs (DMARDs) against p53 wild-type (WT)/mutant-transfected RA fibroblast-like synoviocytes (RAFLSs) was evaluated by MTT assay. Adeno-associated virus (AAV) was employed to establish p53 WT/R211* adjuvant-induced arthritis (AIA) rat model. The arthritic condition of rats was assessed by various parameters such as micro-CT analysis. Knee joint samples were isolated for total RNA sequencing analysis. The expressions of cytokines and immune-related genes were examined by qPCR, ELISA assay and immunofluorescence. The mechanistic pathway was determined by immunoprecipitation and Western blotting in vitro and in vivo. RESULTS: Among p53 mutants, p53R213* exhibited remarkable DMARD-resistance in RAFLSs. However, AAV-induced p53R211* overexpression ameliorated inflammatory arthritis in AIA rats without Methotrexate (MTX)-resistance, and our results discovered the immunomodulatory effect of p53R211* via suppression of T-cell activation and T helper 17 cell (Th17) infiltration in rat joint, and finally downregulated expressions of pro-inflammatory cytokines. Total RNA sequencing analysis identified the correlation of p53R211* with immune-related pathways. Further mechanistic studies revealed that p53R213*/R211* instead of wild-type p53 interacted with TANK-binding kinase 1 (TBK1) and suppressed the innate immune TBK1-Interferon regulatory factor 3 (IRF3)-Stimulator of interferon genes (STING) cascade. CONCLUSIONS: This study unravels the role of p53R213* mutant in RA pathogenesis, and identifies TBK1 as a potential anti-inflammatory target.

Engineering microcracks in MWCNT/elastomer bilayers for high-performance stretchable sensor development.

Stretchable strain sensors in motion detection, health monitoring, and human-machine interfaces are limited by device sensitivity, linearity, hysteresis, stability, and reproducibility in addition to stretchability. Engineering defect structures in sensing material is an effective approach in modulating the material's physical properties, particularly those associated with mechanical responses. Here, we demonstrate that bilayers of carbon nanotubes deposited on an elastomer substrate are mechanically coupled. The microcrack size, density, and distribution in the nanotube thin film can be engineered through uniaxial tensile training to exhibit highly tunable and stable piezoresistive responses with sensitivity, linearity, range, and reproducibility. These responses far exceeding those in uniform metallic films, patterned structures, and composites. In addition, numerical analyses performed on a two-dimensional network model of the cracked nanotube film provide quantitative explanations of how crack configuration, and evolvement under strain, lead to the significant enhancements in stretchable sensor performance using current bilayer structures.

The mediating effect of distress tolerance on the relationship between stressful life events and suicide risk in patients with major depressive disorder.

BACKGROUND: Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD. METHODS: A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk. RESULTS: The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect. CONCLUSION: Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD.

Efficacy and safety of remimazolam tosilate versus propofol in patients undergoing day surgery: a prospective randomized controlled trial.

BACKGROUND: Remimazolam tosilate (RT) is a novel short-acting GABA (A) receptor agonist that has a rapid recovery from procedural sedation and can be fully reversed by flumazenil. To date, there have been relatively few articles comparing RT and propofol for general anesthesia. This study aimed to assess the efficacy and safety of RT with or without flumazenil compared with propofol in general anesthesia for day surgery. METHODS: 115 patients scheduled for day surgery were randomized into three groups: RT (n = 39), RT + flumazenil (n = 38) and propofol (n = 38). The primary endpoints were anesthesia induction time and time until fully alert. Anesthesia success rate, bispectral index (BIS) values, injection pain, opioid and vasopressor dosages, postoperative recovery profiles and perioperative inflammatory and cognitive changes were assessed. Any adverse events were recorded. RESULTS: Induction times were similar among the three groups (P = 0.437), but the median time until fully alert in patients treated with RT was longer than that of the propofol or RT + flumazenil groups (17.6 min vs. 12.3 min vs. 12.3 min, P < 0.001). The three groups had comparable postoperative recovery quality and inflammatory and cognitive state changes (P > 0.05). Smaller percentages of patients who received RT (26.3%) and RT + flumazenil (31.6%) developed hypotension during anesthesia maintenance compared with propofol (68.4%), and consequently less ephedrine (P < 0.001) and phenylephrine (P = 0.015) were needed in the RT group. Furthermore, serum triglyceride levels were lower (P < 0.001) and injection pain was much less frequent in the RT with or without flumazenil groups compared with the propofol group (5.3% vs. 0% vs. 18.4%). CONCLUSION: RT permits rapid induction and comparable recovery profile compared with propofol in general anesthesia for day surgery, but has a prolonged recovery time without flumazenil. The safety profile of RT was superior to propofol in terms of hypotension and injection pain. TRIAL REGISTRATION: The study was registered at Chinese Clinical Trial Registry http://www.chictr.org.cn/ (Registration date: 19/7/2021; Trial ID: ChiCTR2100048904).

Diagnostic Value of Artificial Intelligence-Assistant Diagnostic System Combined With Contrast-Enhanced Ultrasound in Thyroid TI-RADS 4 Nodules.

OBJECTIVES: This study evaluated the diagnostic value of artificial intelligence-assistant diagnostic system combined with contrast-enhanced ultrasound in The American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) 4 category thyroid nodules. METHODS: Thyroid nodules that were evaluated as ACR TI-RADS 4 by conventional ultrasound were selected, all of which had pathological or fine needle aspiration (FNA) results. All nodules were examined by contrast-enhanced ultrasound (CEUS) and artificial intelligence (AI) analysis. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of AI, CEUS and their combined diagnosis were compared; Analyzed and compared the diagnostic efficiency of AI, CEUS and their combined diagnosis. RESULTS: A total of 148 thyroid nodules were included in 140 patients, including 58 malignant nodules and 89 benign nodules. The sensitivity of combined diagnosis was significantly higher than that of AI or CEUS alone (P < .05). The NPV of AI, CEUS and combined diagnosis were statistically significant (P < .05). There was no significant difference in the diagnostic efficacy between AI and CEUS (P > .05), but there was a significant difference in NPV between AI and combined diagnosis (P < .05). The AUC of the combined diagnosis was 0.859, which was higher than that of AI, CEUS alone. CONCLUSIONS: AI has a high diagnostic efficiency, which was helpful for radiologists to make rapid assessment. AI combined CEUS can significantly improve the diagnostic sensitivity and NPV, which was beneficial for the early detection of malignant nodules.

Accelerated discovery of high-performance Al-Si-Mg-Sc casting alloys by integrating active learning with high-throughput CALPHAD calculations.

Scandium is the best alloying element to improve the mechanical properties of industrial Al-Si-Mg casting alloys. Most literature reports devote to exploring/designing optimal Sc additions in different commercial Al-Si-Mg casting alloys with well-defined compositions. However, no attempt to optimize the contents of Si, Mg, and Sc has been made due to the great challenge of simultaneous screening in high-dimensional composition space with limited experimental data. In this paper, a novel alloy design strategy was proposed and successfully applied to accelerate the discovery of hypoeutectic Al-Si-Mg-Sc casting alloys over high-dimensional composition space. Firstly, high-throughput CALculation of PHAse Diagrams (CALPHAD) solidification simulations of ocean of hypoeutectic Al-Si-Mg-Sc casting alloys over a wide composition range were performed to establish the quantitative relation 'composition-process-microstructure'. Secondly, the relation 'microstructure-mechanical properties' of Al-Si-Mg-Sc hypoeutectic casting alloys was acquired using the active learning technique supported by key experiments designed by CALPHAD and Bayesian optimization samplings. After a benchmark in A356-xSc alloys, such a strategy was utilized to design the high-performance hypoeutectic Al-xSi-yMg alloys with optimal Sc additions that were later experimentally validated. Finally, the present strategy was successfully extended to screen the optimal contents of Si, Mg, and Sc over high-dimensional hypoeutectic Al-xSi-yMg-zSc composition space. It is anticipated that the proposed strategy integrating active learning with high-throughput CALPHAD simulations and key experiments should be generally applicable to the efficient design of high-performance multi-component materials over high-dimensional composition space.