Multi-Stimulus Least-Squares Transformation With Online Adaptation Scheme to Reduce Calibration Effort for SSVEP-Based BCIs.

Steady-state visual evoked potential (SSVEP), one of the most popular electroencephalography (EEG)-based brain-computer interface (BCI) paradigms, can achieve high performance using calibration-based recognition algorithms. As calibration-based recognition algorithms are time-consuming to collect calibration data, the least-squares transformation (LST) has been used to reduce the calibration effort for SSVEP-based BCI. However, the transformation matrices constructed by current LST methods are not precise enough, resulting in large differences between the transformed data and the real data of the target subject. This ultimately leads to the constructed spatial filters and reference templates not being effective enough. To address these issues, this paper proposes multi-stimulus LST with online adaptation scheme (ms-LST-OA). METHODS: The proposed ms-LST-OA consists of two parts. Firstly, to improve the precision of the transformation matrices, we propose the multi-stimulus LST (ms-LST) using cross-stimulus learning scheme as the cross-subject data transformation method. The ms-LST uses the data from neighboring stimuli to construct a higher precision transformation matrix for each stimulus to reduce the differences between transformed data and real data. Secondly, to further optimize the constructed spatial filters and reference templates, we use an online adaptation scheme to learn more features of the EEG signals of the target subject through an iterative process trial-by-trial. RESULTS: ms-LST-OA performance was measured for three datasets (Benchmark Dataset, BETA Dataset, and UCSD Dataset). Using few calibration data, the ITR of ms-LST-OA achieved 210.01±10.10 bits/min, 172.31±7.26 bits/min, and 139.04±14.90 bits/min for all three datasets, respectively. CONCLUSION: Using ms-LST-OA can reduce calibration effort for SSVEP-based BCIs.

A bibliometric and visual analysis of cognitive function in bipolar disorder from 2012 to 2022.

INTRODUCTION: Bipolar disorder (BD) is a chronic psychiatric disorder that combines hypomania or mania and depression. The study aims to investigate the research areas associated with cognitive function in bipolar disorder and identify current research hotspots and frontier areas in this field. METHODOLOGY: Publications related to cognitive function in BD from 2012 to 2022 were searched on the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and Scimago Graphica were used to conduct this bibliometric analysis. RESULTS: A total of 989 articles on cognitive function in BD were included in this review. These articles were mainly from the United States, China, Canada, Spain and the United Kingdom. Our results showed that the journal "Journal of Affective Disorders" published the most articles. Apart from "Biploar disorder" and "cognitive function", the terms "Schizophrenia", "Meta analysis", "Rating scale" were also the most frequently used keywords. The research on cognitive function in bipolar disorder primarily focused on the following aspects: subgroup, individual, validation and pathophysiology. CONCLUSIONS: The current concerns and hotspots in the filed are: "neurocognitive impairment", "subgroup", "1st degree relative", "mania", "individual" and "validation". Future research is likely to focus on the following four themes: "Studies of the bipolar disorder and cognitive subgroups", "intra-individual variability", "Validation of cognitive function tool" and "Combined with pathology or other fields".

A High Threshold of Biotherapeutic Aggregate Numbers is Needed to Induce an Immunogenic Response In Vitro, In Vivo, and in the Clinic.

BACKGROUND AND PURPOSE: There is concern that subvisible aggregates in biotherapeutic drug products pose a risk to patient safety. We investigated the threshold of biotherapeutic aggregates needed to induce immunogenic responses. METHODS AND RESULTS: Highly aggregated samples were tested in cell-based assays and induced cellular responses in a manner that depended on the number of particles. The threshold of immune activation varied by disease state (cancer, rheumatoid arthritis, allergy), concomitant therapies, and particle number. Compared to healthy donors, disease state patients showed an equal or lower response at the late phase (7 days), suggesting they may not have a higher risk of responding to aggregates. Xeno-het mice were used to assess the threshold of immune activation in vivo. Although highly aggregated samples (~ 1,600,000 particles/mL) induced a weak and transient immunogenic response in mice, a 100-fold dilution of this sample (~ 16,000 particles/mL) did not induce immunogenicity. To confirm this result, subvisible particles (up to ~ 18,000 particles/mL, containing aggregates and silicone oil droplets) produced under representative administration practices (created upon infusion of a drug product through an IV catheter) did not induce a response in cell-based assays or appear to increase the rate of adverse events or immunogenicity during phase 3 clinical trials. CONCLUSION: The ability of biotherapeutic aggregates to elicit an immune response in vitro, in vivo, and in the clinic depends on high numbers of particles. This suggests that there is a high threshold for aggregates to induce an immunogenic response which is well beyond that seen in standard biotherapeutic drug products.

A zinc finger transcription factor enables social behaviors while controlling transposable elements and immune response in prefrontal cortex.

The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in rodent prefrontal cortex was previously demonstrated to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Following viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, inversion of ZFP189-mediated transcription in this brain area, achieved by viral delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. RNA sequencing of virally manipulated prefrontal cortex tissues reveals that ZFP189 transcription factors of opposing regulatory function (ZFP189WT versus ZFP189VPR) have opposite influence on the expression of genetic transposable elements as well as genes that participate in adaptive immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for complex social behaviors while regulating transposable element-rich regions of DNA and the expression of immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.

Aberrant Functional Connectivity in Core-Periphery Structure Based on WSBM in ADHD.

OBJECTIVE: Brain network studies have revealed that the community structure of ADHD is altered. However, these studies have only focused on modular community structure, ignoring the core-periphery community structure. METHOD: This paper employed the weighted stochastic block model to divide the functional connectivity (FC) into 10 communities. And we adopted core score to define the core-periphery structure of FC. Finally, connectivity strength (CS) and disruption index (DI) were used to evaluate the changes of core-periphery structure in ADHD. RESULTS: The core community of visual network showed reduced CS and a positive value of DI, while the CS of periphery community was enhanced. In addition, the interaction between core communities (involving the sensorimotor and visual network) and periphery community of attention network showed increased CS and a negative valve of DI. CONCLUSION: Anomalies in core-periphery community structure provide a new perspective for understanding the community structure of ADHD.

Enhanced Dynamic Laterality Based on Functional Subnetworks in Patients with Bipolar Disorder.

An ocean of studies have pointed to abnormal brain laterality changes in patients with bipolar disorder (BD). Determining the altered brain lateralization will help us to explore the pathogenesis of BD. Our study will fill the gap in the study of the dynamic changes of brain laterality in BD patients and thus provide new insights into BD research. In this work, we used fMRI data from 48 BD patients and 48 normal controls (NC). We constructed the dynamic laterality time series by extracting the dynamic laterality index (DLI) at each sliding window. We then used k-means clustering to partition the laterality states and the Arenas-Fernandez-Gomez (AFG) community detection algorithm to determine the number of states. We characterized subjects' laterality characteristics using the mean laterality index (MLI) and laterality fluctuation (LF). Compared with NC, in all windows and state 1, BD patients showed higher MLI in the attention network (AN) of the right hemisphere, and AN in the left hemisphere showed more frequent laterality fluctuations. AN in the left hemisphere of BD patients showed higher MLI in all windows and state 3 compared to NC. In addition, in the AN of the right hemisphere in state 1, higher MLI in BD patients was significantly associated with patient symptoms. Our study provides new insights into the understanding of BD neuropathology in terms of brain dynamic laterality.

Histone H1x in mouse ventral hippocampus correlates with, but does not cause behavioral adaptations to stress.

Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrate that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8-10-week-old male C57BL/6J mice were randomly assigned to stressed and unstressed groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced experimental mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or unstressed mice. In sum, although we confirm vHipp protein levels of H1x correlate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are correlated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.

SABRE Hyperpolarization of Exchangeable Protons in Methanol-d4 through Dynamic Covalent Bonds.

Utilizing para-hydrogen (p-H2)-induced hyperpolarization to increase the sensitivity of nuclear magnetic resonance, especially signal amplification by reversible exchange (SABRE), has been widely studied. Here, we achieved hyperpolarization of exchangeable protons in methanol-d4 by introducing dynamic covalent bonds as reversible exchange following the SABRE process. To release the hyperpolarized CD3OH, the pyridine-based ligands with aldehyde groups underwent acetal exchange between the aldehyde and hydroxyl groups of CD3OH after being first hyperpolarized by SABRE. Our mechanistic study highlights the importance of the reversible exchange of functional groups and chemical kinetics in realizing hyperpolarization of exchangeable protons in methanol-d4. Our work broadens SABRE's chemical system compatibility and possible applications.

High-Quality Reconstruction for Laplace NMR Based on Deep Learning.

Laplace nuclear magnetic resonance (NMR) exploits relaxation and diffusion phenomena to reveal information regarding molecular motions and dynamic interactions, offering chemical resolution not accessible by conventional Fourier NMR. Generally, the applicability of Laplace NMR is subject to the performance of signal processing and reconstruction algorithms involving an ill-posed inverse problem. Here, we propose a proof-of-concept of a deep-learning-based method for rapid and high-quality spectra reconstruction from Laplace NMR experimental data. This reconstruction method is performed based on training on synthetic exponentially decaying data, which avoids a vast amount of practically acquired data and makes it readily suitable for one-dimensional relaxation and diffusion measurements by commercial NMR instruments.

A zinc finger transcription factor tunes social behaviors by controlling transposable elements and immune response in prefrontal cortex.

The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in the rodent prefrontal cortex was previously determined to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Upon viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, dysregulation of ZFP189-mediated transcription in this brain area, achieved by delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. By performing RNA sequencing in virally manipulated prefrontal cortex tissues, we discover that ZFP189 transcription factors of opposing regulatory function have opposite influence on the expression of genetic transposable elements as well as genes that participate in immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for social behaviors by binding transposable element-rich regions of DNA to regulate immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.

A flexible speller based on time-space frequency conversion SSVEP stimulation paradigm under dry electrode.

Introduction: Speller is the best way to express the performance of the brain-computer interface (BCI) paradigm. Due to its advantages of short analysis time and high accuracy, the SSVEP paradigm has been widely used in the BCI speller system based on the wet electrode. It is widely known that the wet electrode operation is cumbersome and that the subjects have a poor experience. In addition, in the asynchronous SSVEP system based on threshold analysis, the system flickers continuously from the beginning to the end of the experiment, which leads to visual fatigue. The dry electrode has a simple operation and provides a comfortable experience for subjects. The EOG signal can avoid the stimulation of SSVEP for a long time, thus reducing fatigue. Methods: This study first designed the brain-controlled switch based on continuous blinking EOG signal and SSVEP signal to improve the flexibility of the BCI speller. Second, in order to increase the number of speller instructions, we designed the time-space frequency conversion (TSFC) SSVEP stimulus paradigm by constantly changing the time and space frequency of SSVEP sub-stimulus blocks, and designed a speller in a dry electrode environment. Results: Seven subjects participated and completed the experiments. The results showed that the accuracy of the brain-controlled switch designed in this study was up to 94.64%, and all the subjects could use the speller flexibly. The designed 60-character speller based on the TSFC-SSVEP stimulus paradigm has an accuracy rate of 90.18% and an information transmission rate (ITR) of 117.05 bits/min. All subjects can output the specified characters in a short time. Discussion: This study designed and implemented a multi-instruction SSVEP speller based on dry electrode. Through the combination of EOG and SSVEP signals, the speller can be flexibly controlled. The frequency of SSVEP stimulation sub-block is recoded in time and space by TSFC-SSVEP stimulation paradigm, which greatly improves the number of output instructions of BCI system in dry electrode environment. This work only uses FBCCA algorithm to test the stimulus paradigm, which requires a long stimulus time. In the future, we will use trained algorithms to study stimulus paradigm to improve its overall performance.

Altered higher-order coupling between brain structure and function with embedded vector representations of connectomes in schizophrenia.

It has been shown that the functional dependency of the brain exists in both direct and indirect regional relationships. Therefore, it is necessary to map higher-order coupling in brain structure and function to understand brain dynamic. However, how to quantify connections between not directly regions remains unknown to schizophrenia. The word2vec is a common algorithm through create embeddings of words to solve these problems. We apply the node2vec embedding representation to characterize features on each node, their pairwise relationship can give rise to correspondence relationships between brain regions. Then we adopt pearson correlation to quantify the higher-order coupling between structure and function in normal controls and schizophrenia. In addition, we construct direct and indirect connections to quantify the coupling between their respective functional connections. The results showed that higher-order coupling is significantly higher in schizophrenia. Importantly, the anomalous cause of coupling mainly focus on indirect structural connections. The indirect structural connections play an essential role in functional connectivity-structural connectivity (SC-FC) coupling. The similarity between embedded representations capture more subtle network underlying information, our research provides new perspectives for understanding SC-FC coupling. A strong indication that the structural backbone of the brain has an intimate influence on the resting-state functional.

Gender effects on the controllability of hemispheric white matter networks.

Male and female adults exhibited significant group differences in brain white matter (WM) asymmetry and WM network controllability. However, gender differences in controllability of hemispheric WM networks between males and females remain to be determined. Based on 1 principal atlas and 1 replication atlas, this work characterized the average controllability (AC) and modal controllability (MC) of hemispheric WM network based on 1 principal dataset and 2 replication datasets. All results showed that males had higher AC of left hemispheric networks than females. And significant hemispheric asymmetry was revealed in regional AC and MC. Furthermore, significant gender differences in the AC asymmetry were mainly found in regions lie in the frontoparietal network, and the MC asymmetry was found in regions involving auditory and emotion process. Finally, we found significant associations between regional controllability and cognitive features. Taken together, this work could provide a novel perspective for understanding gender differences in hemispheric WM asymmetry and cognitive function between males and females.

Abnormal dynamic reconfiguration of the large-scale functional network in schizophrenia during the episodic memory task.

Episodic memory deficits are the core feature in schizophrenia (SCZ). Numerous studies have revealed abnormal brain activity associated with this disorder during episodic memory, however previous work has only relied on static analysis methods that treat the brain as a static monolithic structure, ignoring the dynamic features at different time scales. Here, we applied dynamic functional connectivity analysis to functional magnetic resonance imaging data during episodic memory and quantify integration and recruitment metrics to reveal abnormal dynamic reconfiguration of brain networks in SCZ. In the specific frequency band of 0.06-0.125 Hz, SCZ showed significantly higher integration during encoding and retrieval, and the abnormalities were mainly in the default mode, frontoparietal, and cingulo-opercular modules. Recruitment of SCZ was significantly higher during retrieval, mainly in the visual module. Interestingly, interactions between groups and task status in recruitment were found in the dorsal attention, visual modules. Finally, we observed that integration was significantly associated with memory performance in frontoparietal regions. Our findings revealed the time-varying evolution of brain networks in SCZ, while improving our understanding of cognitive decline and other pathophysiologies in brain diseases.

Abnormal information interaction in multilayer directed network based on cross-frequency integration of mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been reported to result in abnormal cross-frequency integration. However, previous studies have failed to consider specific abnormalities in receiving and outputting information among frequency bands during integration. Here, we investigated heterogeneity in receiving and outputting information during cross-frequency integration in patients. The results showed that during cross-frequency integration, information interaction first increased and then decreased, manifesting in the heterogeneous distribution of inter-frequency nodes for receiving information. A possible explanation was that due to damage to some inter-frequency hub nodes, intra-frequency nodes gradually became new inter-frequency nodes, whereas original inter-frequency nodes gradually became new inter-frequency hub nodes. Notably, damage to the brain regions that receive information between layers was often accompanied by a strengthened ability to output information and the emergence of hub nodes for outputting information. Moreover, an important compensatory mechanism assisted in the reception of information in the cingulo-opercular and auditory networks and in the outputting of information in the visual network. This study revealed specific abnormalities in information interaction and compensatory mechanism during cross-frequency integration, providing important evidence for understanding cross-frequency integration in patients with MCI and AD.

Abnormal Spatial and Temporal Overlap of Time-Varying Brain Functional Networks in Patients with Schizophrenia.

Schizophrenia (SZ) is a complex psychiatric disorder with unclear etiology and pathological features. Neuroscientists are increasingly proposing that schizophrenia is an abnormality in the dynamic organization of brain networks. Previous studies have found that the dynamic brain networks of people with SZ are abnormal in both space and time. However, little is known about the interactions and overlaps between hubs of the brain underlying spatiotemporal dynamics. In this study, we aimed to investigate different patterns of spatial and temporal overlap of hubs between SZ patients and healthy individuals. Specifically, we obtained resting-state functional magnetic resonance imaging data from the public dataset for 43 SZ patients and 49 healthy individuals. We derived a representation of time-varying functional connectivity using the Jackknife Correlation (JC) method. We employed the Betweenness Centrality (BC) method to identify the hubs of the brain's functional connectivity network. We then applied measures of temporal overlap, spatial overlap, and hierarchical clustering to investigate differences in the organization of brain hubs between SZ patients and healthy controls. Our findings suggest significant differences between SZ patients and healthy controls at the whole-brain and subnetwork levels. Furthermore, spatial overlap and hierarchical clustering analysis showed that quasi-periodic patterns were disrupted in SZ patients. Analyses of temporal overlap revealed abnormal pairwise engagement preferences in the hubs of SZ patients. These results provide new insights into the dynamic characteristics of the network organization of the SZ brain.

Research on smooth path planning method based on improved ant colony algorithm optimized by Floyd algorithm.

Aiming at the problems of slow convergence and easy fall into local optimal solution of the classic ant colony algorithm in path planning, an improved ant colony algorithm is proposed. Firstly, the Floyd algorithm is introduced to generate the guiding path, and increase the pheromone content on the guiding path. Through the difference in initial pheromone, the ant colony is guided to quickly find the target node. Secondly, the fallback strategy is applied to reduce the number of ants who die due to falling into the trap to increase the probability of ants finding the target node. Thirdly, the gravity concept in the artificial potential field method and the concept of distance from the optional node to the target node are introduced to improve the heuristic function to make up for the fallback strategy on the convergence speed of the algorithm. Fourthly, a multi-objective optimization function is proposed, which comprehensively considers the three indexes of path length, security, and energy consumption and combines the dynamic optimization idea to optimize the pheromone update method, to avoid the algorithm falling into the local optimal solution and improve the comprehensive quality of the path. Finally, according to the connectivity principle and quadratic B-spline curve optimization method, the path nodes are optimized to shorten the path length effectively.

An open-label non-inferiority randomized trail comparing the effectiveness and safety of ultrasound-guided selective cervical nerve root block and fluoroscopy-guided cervical transforaminal epidural block for cervical radiculopathy.

OBJECT: To compare therapeutic efficacy and safety of ultrasound (US)-guided selective nerve root block (SNRB) and fluoroscopy (FL)-guided transforaminal epidural steroid injection (TFESI) for cervical spine radiculopathy (CSR). METHOD: 156 patients with CSR randomly received US-guided SNRB verified by FL or FL-guided TFESI. We hypothesised that the accuracy rate of contrast dispersion into epidural or intervertebral foraminal space in the US group was not inferior to that in the FL group with a margin of clinical unimportance of -15%. Pain intensity assessed by Numeric Rating Scales (NRS) and functional disability estimated by neck disability index (NDI) were compared before treatment, at 1, 3 and 6 months after the intervention. Puncture time and complication frequencies were also reported. RESULTS: 88.7% and 90.3% accuracy ratings were respectively achieved in the US and FL groups with a treatment difference of -1.6% (95%CI: -9.7%, 6.6%) revealing that the lower limit was above the non-inferiority margin. Both NRS and NDI scores illustrated improvements at 1, 3 and 6 months after intervention with no statistically significant differences between the two groups (all p > .05). Additionally, shorter administration duration was observed in the US group (p < .001). No severe complications were observed in both group. CONCLUSION: Compared with the FL group, the US group provided a non-inferior accuracy rate of epidural/foraminal contrast pattern. For the treatment of CSR, the US technique provided similar pain relief and functional improvements while facilitating distinguishing critical vessels adjacent to the foramen and requiring a shorter procedure duration without exposure to radiation. Therefore, it was an attractive alternative to the conventional FL method.Key messagesWe conducted a prospective, open-label, randomised and non-inferiority clinical trial to estimate a hypothesis that the precisely accurate delivery through ultrasound (US)-guided cervical selective nerve root block (SNRB) was non-inferior to that using FL-guided transforaminal epidural steroid injection. Additionally, US-guided SNRB was as effective as FL-guided TFESI in the treatment effect on pain relief and function improvements. Notably, the US technique might be an alternative to the conventional FL method due to the ability to prevent inadvertent vascular puncture (VP) and intravascular injection (IVI) with a shorter administration time and absence of radiation exposure.

Mechanism of the Micellar Solubilization of Curcumin by Mixed Surfactants of SDS and Brij35 via NMR Spectroscopy.

The micellar solubilization mechanism of curcumin by mixed surfactants of SDS and Brij35 was investigated at the molecular scale by NMR spectroscopy. Through the investigation of the micelle formation process, types and structures of mixed micelles and solubilization sites, the intrinsic factors influencing the solubilization capacity were revealed. For systems with αSDS = 0.5 and 0.2, the obtained molar solubilization ratios (MSRs) are consistent with the MSRideal values. However, for αSDS = 0.8, the solubilization capacity of curcumin is weakened compared to the MSRideal. Furthermore, only one single mixed SDS/Brij35 micelles are formed for αSDS = 0.5 and 0.2. However, for αSDS = 0.8, there are separate SDS-rich and Brij35-rich mixed micelles formed. In addition, NOESY spectra show that the interaction patterns of SDS and Brij35 in mixed micelles are similar for three systems, as are the solubilization sites of curcumin. Therefore, for αSDS = 0.5 and 0.2 with single mixed micelles formed, the solubility of curcumin depends only on the mixed micelle composition, which is almost equal to the surfactant molar ratio. Although curcumin is solubilized in both separate micelles at αSDS = 0.8, a less stable micelle structure may be responsible for the low solubility. This study provides new insights into the investigation and application of mixed micelle solubilization.

Identification of m6A- and ferroptosis-related lncRNA signature for predicting immune efficacy in hepatocellular carcinoma.

Background: N6-methyladenosine (m6A) methylation and ferroptosis assist long noncoding RNAs (lncRNAs) in promoting immune escape in hepatocellular carcinoma (HCC). However, the predictive value of m6A- and ferroptosis-related lncRNAs (mfrlncRNAs) in terms of immune efficacy remains unknown. Method: A total of 365 HCC patients with complete data from The Cancer Genome Atlas (TCGA) database were used as the training cohort, and half of them were randomly selected as the validation cohort. A total of 161 HCC patients from the International Cancer Genome Consortium (ICGC) database were used as external validation (ICGC cohort). Results: We first identified a group of specific lncRNAs associated with both m6A regulators and ferroptosis-related genes and then constructed prognosis-related mfrlncRNA pairs. Based on this, the mfrlncRNA signature was constructed using the least absolute shrinkage and selection operator (LASSO) analysis and Cox regression. Notably, the risk score of patients was proven to be an independent prognostic factor and was better than the TNM stage and tumor grade. Moreover, patients with high-risk scores had lower survival rates, higher infiltration of immunosuppressive cells (macrophages and Tregs), lower infiltration of cytotoxic immune cells (natural killer cells), poorer immune efficacy (both immunophenoscore and score of tumor immune dysfunction and exclusion), higher IC50, and enrichment of the induced Treg pathway, which confirmed that the mfrlncRNA signature contributed to survival prediction and risk stratification of patients with HCC. Conclusions: The mfrlncRNA signature, which has great prognostic value, provides new clues for identifying "cold" and "hot" tumors and might have crucial implications for individualized therapy to improve the survival rate of patients with HCC.