Analysis of barriers associated with emergency medical service activation in patients with acute stroke and acute myocardial infarction from Zhongjiang County of Sichuan Province in China.

OBJECTIVES: The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances. METHODS: We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people's hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression. RESULTS: we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient's son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient's partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use. CONCLUSION: There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities.

Research Progress in the Field of Tumor Model Construction Using Bioprinting: A Review.

The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.

Scalp acupuncture guidance for identifying the optimal site for transcranial electrical stimulation of the hand.

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.

Hyperhomocysteinemia is associated with the risk of venous thromboembolism in patients with mental illness: a case-control study.

Objective: The risk of venous thromboembolism in patients with mental illness has been insufficiently addressed. This study aimed to assess the correlation between hyperhomocysteinemia and venous thromboembolism prevalence among this population. Methods: Patients with a diagnosis of mental illness and concurrent venous thromboembolism, admitted to Sir Run Run Shaw Hospital at Zhejiang University School of Medicine between January 2014 and December 2021, were included in the venous thromboembolism group. The control group, approximately twice the size, comprised individuals with mental illness but without venous thromboembolism. Basic clinical data were gathered for both cohorts. Results: In psychiatric patients, elevated D-dimer levels(OR=5.60,95% CI 3.28-10.00), hyperhomocysteinemia (OR=2.37,95% CI 1.10-5.14), and hyperprolactinemia(OR= 2.68,95% CI 1.12-6.42)were significant risk factors for venous thromboembolism. According to further subgroup analyses, hyperhomocysteinemia is a significant risk factor associated with pulmonary embolism, with an OR of 5.08 (95% CI 1.20-21.48). An interaction effect between gender and homocysteine level was found, with a p-interaction of 0.022. A subsequent analysis confirmed the association between hyperhomocysteinemia and venous thromboembolism in female psychiatric patients, with an OR of 3.34 (95% CI 1.68-6.65), indicating that hyperhomocysteinemia is a significant risk factor for venous thromboembolism in women. Conclusion: Patients with psychiatric disorders were found to have an elevated risk of venous thromboembolism, which was associated with increased levels of D-dimer, hyperprolactinemia, and hyperhomocysteinemia. A strong correlation between hyperhomocysteinemia and pulmonary embolism was identified in patients with mental illnesses. Furthermore, the study revealed that female psychiatric patients with hyperhomocysteinemia constituted a high-risk group for venous thromboembolism. This finding holds significant clinical implications, suggesting that early preventative measures could be implemented for this high-risk population to reduce the incidence of thromboembolic events during hospitalization for psychiatric patients.

Themis: advancing precision oncology through comprehensive molecular subtyping and optimization.

Recent advances in tumor molecular subtyping have revolutionized precision oncology, offering novel avenues for patient-specific treatment strategies. However, a comprehensive and independent comparison of these subtyping methodologies remains unexplored. This study introduces 'Themis' (Tumor HEterogeneity analysis on Molecular subtypIng System), an evaluation platform that encapsulates a few representative tumor molecular subtyping methods, including Stemness, Anoikis, Metabolism, and pathway-based classifications, utilizing 38 test datasets curated from The Cancer Genome Atlas (TCGA) and significant studies. Our self-designed quantitative analysis uncovers the relative strengths, limitations, and applicability of each method in different clinical contexts. Crucially, Themis serves as a vital tool in identifying the most appropriate subtyping methods for specific clinical scenarios. It also guides fine-tuning existing subtyping methods to achieve more accurate phenotype-associated results. To demonstrate the practical utility, we apply Themis to a breast cancer dataset, showcasing its efficacy in selecting the most suitable subtyping methods for personalized medicine in various clinical scenarios. This study bridges a crucial gap in cancer research and lays a foundation for future advancements in individualized cancer therapy and patient management.

EEG emotion recognition based on data-driven signal auto-segmentation and feature fusion.

Pattern recognition based on network connections has recently been applied to the brain-computer interface (BCI) research, offering new ideas for emotion recognition using Electroencephalogram (EEG) signal. However unified standards are currently lacking for selecting emotional signals in emotion recognition research, and potential associations between activation differences in brain regions and network connectivity pattern are often being overlooked. To bridge this technical gap, a data-driven signal auto-segmentation and feature fusion algorithm (DASF) is proposed in this paper. First, the Phase Locking Value (PLV) method was used to construct the brain functional adjacency matrix of each subject, and the dynamic brain functional network across subjects was then constructed. Next, tucker decomposition was performed and the Grassmann distance of the connectivity submatrix was calculated. Subsequently, different brain network states were distinguished and signal segments under emotional states were automatically extract using data-driven methods. Then, tensor sparse representation was adopted on the intercepted EEG signals to effectively extract functional connections under different emotional states. Finally, power-distribution related features (differential entropy and energy feature) and brain functional connection features were effectively combined for classification using the support vector machines (SVM) classifier. The proposed method was validated on ERN and DEAP datasets. The single-feature emotion classification accuracy of 86.57 % and 87.74 % were achieved on valence and arousal dimensions, respectively. The accuracy of the proposed feature fusion method was achieved at 89.14 % and 89.65 %, accordingly, demonstrating an improvement in emotion recognition accuracy. The results demonstrated the superior classification performance of the proposed data-driven signal auto-segmentation and feature fusion algorithm in emotion recognition compared to state-of-the-art classification methods.

Modulating Inter-Muscular Coordination Patterns in the Upper Extremity Induces Changes to Inter-Muscular, Cortico-Muscular, and Cortico-Cortical Connectivity.

OBJECTIVE: The changes in neural drive to muscles associated with modulation of inter-muscular coordination in the upper extremity have not yet been investigated. Such information could help elucidate the neural mechanisms behind motor skill learning. METHODS: Six young, neurologically healthy participants underwent a six-week training protocol to decouple two synergist elbow flexor muscles as a newly learned motor skill in the isometric force generation in upward and medial directions. Concurrent electroencephalography and surface electromyography from twelve upper extremity muscles were recorded in two conditions (As-Trained & Habitual) across two assessments (Week 0 vs. Week 6). Changes to inter-muscular connectivity (IMC), functional muscle networks, cortico-muscular connectivity (CMC), cortico-cortical connectivity (CCC) as well as functional brain network controllability (FBNC) associated with the modulation of inter-muscular coordination patterns were assessed to provide a perspective on the neural mechanisms for the newly learned motor skills. RESULTS: Significant decreases in elbow flexor IMC, CMC, and increases in CCC were observed. No significant changes were observed for FBNC. CONCLUSION: The results of this study suggest that modulating the inter-muscular coordination of the elbow flexor muscle synergy during isometric force generation is associated with multiple yet distinct changes in functional connectivity across the central and peripheral perspectives. SIGNIFICANCE: Understanding the neural mechanisms of modulating inter-muscular coordination patterns can help inform motor rehabilitation regimens.

Neurovascular Coupling Analysis Based on Multivariate Variational Gaussian Process Convergent Cross-Mapping.

Neurovascular coupling (NVC) provides important insights into the intricate activity of brain functioning and may aid in the early diagnosis of brain diseases. Emerging evidences have shown that NVC could be assessed by the coupling between electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). However, this endeavor presents significant challenges due to the absence of standardized methodologies and reliable techniques for coupling analysis of these two modalities. In this study, we introduced a novel method, i.e., the collaborative multi-output variational Gaussian process convergent cross-mapping (CMVGP-CCM) approach to advance coupling analysis of EEG and fNIRS. To validate the robustness and reliability of the CMVGP-CCM method, we conducted extensive experiments using chaotic time series models with varying noise levels, sequence lengths, and causal driving strengths. In addition, we employed the CMVGP-CCM method to explore the NVC between EEG and fNIRS signals collected from 26 healthy participants using a working memory (WM) task. Results revealed a significant causal effect of EEG signals, particularly the delta, theta, and alpha frequency bands, on the fNIRS signals during WM. This influence was notably observed in the frontal lobe, and its strength exhibited a decline as cognitive demands increased. This study illuminates the complex connections between brain electrical activity and cerebral blood flow, offering new insights into the underlying NVC mechanisms of WM.

Exploring the Prospects of Transcranial Electrical Stimulation (tES) as a Therapeutic Intervention for Post-Stroke Motor Recovery: A Narrative Review.

INTRODUCTION: Stroke survivors often have motor impairments and related functional deficits. Transcranial Electrical Stimulation (tES) is a rapidly evolving field that offers a wide range of capabilities for modulating brain function, and it is safe and inexpensive. It has the potential for widespread use for post-stroke motor recovery. Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS) are three recognized tES techniques that have gained substantial attention in recent years but have different mechanisms of action. tDCS has been widely used in stroke motor rehabilitation, while applications of tACS and tRNS are very limited. The tDCS protocols could vary significantly, and outcomes are heterogeneous. PURPOSE: the current review attempted to explore the mechanisms underlying commonly employed tES techniques and evaluate their prospective advantages and challenges for their applications in motor recovery after stroke. CONCLUSION: tDCS could depolarize and hyperpolarize the potentials of cortical motor neurons, while tACS and tRNS could target specific brain rhythms and entrain neural networks. Despite the extensive use of tDCS, the complexity of neural networks calls for more sophisticated modifications like tACS and tRNS.

Enhancing cross-subject EEG emotion recognition through multi-source manifold metric transfer learning.

Transfer learning (TL) has demonstrated its efficacy in addressing the cross-subject domain adaptation challenges in affective brain-computer interfaces (aBCI). However, previous TL methods usually use a stationary distance, such as Euclidean distance, to quantify the distribution dissimilarity between two domains, overlooking the inherent links among similar samples, potentially leading to suboptimal feature mapping. In this study, we introduced a novel algorithm called multi-source manifold metric transfer learning (MSMMTL) to enhance the efficacy of conventional TL. Specifically, we first selected the source domain based on Mahalanobis distance to enhance the quality of the source domains and then used manifold feature mapping approach to map the source and target domains on the Grassmann manifold to mitigate data drift between domains. In this newly established shared space, we optimized the Mahalanobis metric by maximizing the inter-class distances while minimizing the intra-class distances in the target domain. Recognizing that significant distribution discrepancies might persist across different domains even on the manifold, to ensure similar distributions between the source and target domains, we further imposed constraints on both domains under the Mahalanobis metric. This approach aims to reduce distributional disparities and enhance the electroencephalogram (EEG) emotion recognition performance. In cross-subject experiments, the MSMMTL model exhibits average classification accuracies of 88.83 % and 65.04 % for SEED and DEAP, respectively, underscoring the superiority of our proposed MSMMTL over other state-of-the-art methods. MSMMTL can effectively solve the problem of individual differences in EEG-based affective computing.

Corticospinal and corticoreticulospinal projections benefit motor behaviors in chronic stroke.

After corticospinal tract (CST) stroke, several motor deficits in the upper extremity (UE) emerge, including diminished muscle strength, motor control, and muscle individuation. Both the ipsilesional CST and contralesional corticoreticulospinal tract (CReST) innervate the paretic UE and may have different innervation patterns for the proximal and distal UE segments. These patterns may underpin distinct pathway relationships to separable motor behaviors. In this cross-sectional study of 15 chronic stroke patients and 28 healthy subjects, we examined two key questions: (1) whether segmental motor behaviors differentially relate to ipsilesional CST and contralesional CReST projection strengths, and (2) whether motor behaviors segmentally differ in the paretic UE. We measured strength, motor control, and muscle individuation in a proximal (biceps, BIC) and distal muscle (first dorsal interosseous, FDI) of the paretic UE. We measured the projection strengths of the ipsilesional CST and contralesional CReST to these muscles using transcranial magnetic stimulation (TMS). Stroke subjects had abnormal motor control and muscle individuation despite strength comparable to healthy subjects. In stroke subjects, stronger ipsilesional CST projections were linked to superior motor control in both UE segments, whereas stronger contralesional CReST projections were linked to superior muscle strength and individuation in both UE segments. Notably, both pathways also shared associations with behaviors in the proximal segment. Motor control deficits were segmentally comparable, but muscle individuation was worse for distal motor performance. These results suggest that each pathway has specialized contributions to chronic motor behaviors but also work together, with varying levels of success in supporting chronic deficits. Key points summary: Individuals with chronic stroke typically have deficits in strength, motor control, and muscle individuation in their paretic upper extremity (UE). It remains unclear how these altered behaviors relate to descending motor pathways and whether they differ by proximal and distal UE segment.In this study, we used transcranial magnetic stimulation (TMS) to examine projection strengths of the ipsilesional corticospinal tract (CST) and contralesional corticoreticulospinal tract (CReST) with respect to quantitated motor behaviors in chronic stroke.We found that stronger ipsilesional CST projections were associated with better motor control in both UE segments, whereas stronger contralesional CReST projections were associated with better strength and individuation in both UE segments. In addition, projections of both pathways shared associations with motor behaviors in the proximal UE segment.We also found that deficits in strength and motor control were comparable across UE segments, but muscle individuation was worse with controlled movement in the distal UE segment.These results suggest that the CST and CReST have specialized contributions to chronic motor behaviors and also work together, although with different degrees of efficacy.

Examining the wound healing potential of curcumin-infused electrospun nanofibers from polyglutamic acid and gum arabic.

Advancements in medicine have led to continuous enhancements and innovations in wound dressing materials, making them pivotal in medical care. We used natural biological macromolecules, γ-polyglutamic acid and gum arabic as primary raw materials to create nanofibers laden with curcumin by blending electrostatic spinning technology in the current investigation. These nanofibers were meticulously characterized using fluorescence microscopy, scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Our comprehensive analyses confirmed the successful encapsulation of curcumin within the nanofiber carrier and it has uniform diameter, good water absorption and mechanical properties. Subsequently, we evaluated the antimicrobial effects of these curcumin-loaded nanofibers against Staphylococcus aureus through an oscillating flask method. We created a mouse model with acute full-thickness skin defects to further investigate the wound healing potential. We conducted various biochemical assays to elucidate the mechanism of action. The results revealed that curcumin nanofibers profoundly impacted wound healing. They bolstered the expression of TGF-ß1 and VEGF and reduced the expression of inflammatory factors, leading to an accelerated re-epithelialization process, enhanced wound contraction, and increased regeneration of new blood vessels and hair follicles. Furthermore, these nanofibers positively influenced the proportion of three different collagen types. This comprehensive study underscores the remarkable potential of curcumin-loaded nanofibers to facilitate wound healing and lays a robust experimental foundation for developing innovative, natural product-based wound dressings.

Optimization of ultrasound-assisted extraction of Imperata cylindrica polysaccharides and evaluation of its anti-oxidant and amelioration of uric acid stimulated cell apoptosis.

An efficient, cost-effective and environmentally friendly ultrasound-assisted hot water method for Imperata cylindrica polysaccharide (ICPs) extraction was developed. According to the response surface results, the optimal ultrasonic time was 85 min, ultrasonic power was 192.75 W, temperature was 90.74 °C, liquid-solid ratio was 26.1, and polysaccharide yield was 28.50 %. The polysaccharide mainly consisted of arabinose (Ara), galactose (Gal), and glucose (Glc), with a molecular weight of 62.3 kDa. Ultrasound-assisted extraction of Imperata cylindrica polysaccharide (UICP) exhibited stronger anti-oxidant activity and ability to ameliorate cellular damage due to uric acid stimulation compared with traditional hot water extraction of Imperata cylindrica polysaccharide (ICPC-b). It also exhibited higher thermal stability, indicating its potential value for applications in the food industry.

Comparison of ureteral stone measurements for predicting the efficacy of a single session of extracorporeal shockwave lithotripsy: one-, two-, and three-dimensional computed tomography measurements.

The objective of this study was to compare the value of one-, two- and three-dimensional computed tomography (CT) measurements for predicting the efficacy of a single session of extracorporeal shock wave lithotripsy (ESWL) in patients with a single ureteral stone. A total of 165 patients were included based on the inclusion and exclusion criteria. Different models were constructed using a combination of patients' clinical data and measurements obtained by manual sketching and automated extraction software. Multivariate logistic regression was used to develop the models. Receiver operating characteristic curves were used to assess the performance of the models. There was good interobserver agreement for all measurements in different dimensions (P < 0.001). We also found that hydronephrosis, the largest diameter, the largest area, volume, and mean CT value were significantly greater in the failure group than in the success group (P < 0.01). Furthermore, all sizes and CT measurement values were found to be independent predictors for predicting efficacy after one session of ESWL (P < 0.05). In addition, the multivariate logistic analysis showed that the area under the curve (AUC) for two-dimensional and three-dimensional measurements was superior to that of one-dimensional measurement (P < 0.01). However, when size alone was included as a measurable predictor, there was no significant difference in the AUC among the one-, two-, and three-dimensional measurements (P > 0.05). In summary, after adjusting for clinical data, two- and three-dimensional measurements combining ureteral stone size and CT values were found to be the best predictors of ESWL efficacy, and software-based three-dimensional measurements should be considered to avoid interobserver variability in clinical practice.

Fraxin Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation and TLR4/NF-κB and MAPK Signaling Pathways.

Objective: UC is a chronic gastrointestinal disorder of uncertain etiology. However, effective therapeutic drug options for UC are relatively limited. Fraxin represents a principal active constituent within the traditional Chinese medicinal herb known as Cortex Fraxini or Qinpi. Nevertheless, the impact of Fraxin on UC remains uncharted. This study aims to explore the potential of Fraxin, a key component of Cortex Fraxini, in inhibiting DSS-induced intestinal inflammation in mice and to unravel the underlying mechanisms. Methods: In vitro experiment,the RAW264. 7 cells were induced by LPS as the model.In vivo experiment,the mice were induced by DSS as the animal model for a ten day experiment.The ELISA, western blots, measurement of oxidative stress markers and other relevant methods were used to discuss the effect of Fraxin on LPS-induced RAW264.7 cells and the inhibitory effect of Fraxin on intestinal inflammation induced by DSS in mice and underlying mechanisms. Results: Our findings indicated that Fraxin significantly reduced symptoms of UC, such as body weight loss, colonic length shortening, and histological damage. At the molecular level, it inhibited ROS generation, reduced pro-inflammatory cytokines, and regulated key pathways including TLR4/NF-κB and MAPK.The findings indicated that Fraxin diminished the expression of p-NF-κB and p-IκB, downregulated iNOS and COX-2 expression, and lessened p38, JNK and ERK phosphorylation. Conclusion: Taken together, Fraxin ameliorates UC by regulating oxidative stress, inflammation, and TLR4/NF-κB and MAPK pathways, and Fraxin may be a new treatment for UC. Our findings suggest that Fraxin could offer a novel therapeutic approach for UC, targeting oxidative stress and key inflammatory pathways.

CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia.

BACKGROUND: Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells. In response, this study aims to enhance CD19 CAR-NK cell efficacy and mitigate the risk of tumor recurrence due to target antigen escape by developing CD19 and CD20 (CD19/CD20) dual-targeted CAR-NK cells. METHODS: Initially, mRNA encoding anti-CD19 CARs (FMC63 scFv-CD8α-4-1BB-CD3ζ) and anti-CD20 CARs (LEU16 scFv-CD8α-4-1BB-CD3ζ) was constructed via in vitro transcription. Subsequently, CD19/CD20 dual-targeted CAR-NK cells were generated through simultaneous electrotransfection of CD19/CD20 CAR mRNA into umbilical cord blood-derived NK cells (UCB-NK). RESULTS: Following co-electroporation, the percentage of dual-CAR expression on NK cells was 86.4% ± 1.83%, as determined by flow cytometry. CAR expression was detectable at 8 h post-electric transfer, peaked at 24 h, and remained detectable at 96 h. CD19/CD20 dual-targeted CAR-NK cells exhibited increased specific cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines (BALL-1: CD19+CD20+, REH: CD19+CD20-, Jurkat: CD19-CD20-) compared to UCB-NK, CD19 CAR-NK, and CD20 CAR-NK cells. Moreover, CD19/CD20 dual-targeted CAR-NK cells released elevated levels of perforin, IFN-γ, and IL-15. Multiple activation markers such as CD69 and cytotoxic substances were highly expressed. CONCLUSIONS: The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment.

Analyst optimism, information disclosure, and stock price collapse risk: Empirical insights from China's A-share market.

This study selects stock data of listed companies in China's A-share stock market from 2011 to 2020 as research samples. Using a fixed-effects model, it examines the impact of analyst optimism on stock price collapses and the moderating effect of information disclosure quality. Simultaneously, it conducts additional research to explore the potential transmission mechanisms involved. The main findings are as follows: Firstly, a positive correlation exists between analyst optimism and the risk of stock price collapse. Secondly, improving information disclosure quality of listed companies can enhance the positive impact of analyst optimism on the risk of stock price collapses and expedite the market's adjustment of overly optimistic valuations of listed companies. Additionally, analyst optimism can increase the risk of stock price collapses by affecting institutional ownership. These findings provide theoretical support for regulatory authorities to revise and improve the "information disclosure evaluation" system, regulate the analyst industry, guide analyst behavior, and encourage listed companies to enhance internal governance and improve information disclosure practices.

Development and validation of a general-purpose ReaxFF reactive force field for earth material modeling.

ReaxFF reactive force field bridges the gap between nonreactive molecular simulations and quantum mechanical calculations and has been widely applied during the past two decades. However, its application to earth materials, especially those under high T-P conditions relevant to Earth's interior, is still limited due to the lack of available parameters. Here, we present the development and validation of a ReaxFF force field containing several of the most common elements in Earth's crust, i.e., Si/Al/O/H/Na/K. The force field was trained against a large data set obtained from density functional theory (DFT) calculations, including charges, bond/angle distortion curves, equation of states, ion migration energy profiles, and condensation reaction energies. Different coordination environments were considered in the training set. The fitting results showed that the current force field can well reproduce the DFT data (the Pearson correlation coefficient, Rp, is 0.95). We validated the force field on mineral-water interfaces, hydrous melts/supercritical geofluids, and bulk crystals. It was found that the current force field performed excellently in predicting the structural, thermodynamic, and transport properties of various systems (Rp = 0.95). Moreover, possible applications and future development have been discussed. The results obtained in this study suggest that the current force field holds good promise to model a wide range of processes and thus open opportunities to advance the application of ReaxFF in earth material modeling.