Impact of using virtual avatars in educational videos on user experience.

Popularization of knowledge is of considerable importance and necessity, and traditional knowledge popularization activities suffer from high cost and low acceptance, which affect their effectiveness and coverage. Applying virtual avatars to educational videos may be an effective way to solve the problem. This study investigates the impact of applying virtual avatars to educational videos on user experience. Constructed a model of the impact of user experience on educational videos with virtual avatars, collected data from the target population, and analyzed it empirically. The video quality and virtual avatar expressiveness dimensions of the influencing factors have a significant positive effect on the learning effect, emotional experience and user engagement dimensions of user experience; the content quality dimension of the influencing factors has a significant negative effect on the three dimensions of user experience. The video quality and virtual avatar expressiveness dimensions of the influencing factors have a significant positive effect on the learning effect, emotional experience and user engagement dimensions of user experience; the content quality dimension of the influencing factors has a significant negative effect on the three dimensions of user experience.

Effects of Rhizopus-arrhizus-31-Assisted Pretreatment on the Extraction and Bioactivity of Total Flavonoids from Hibiscus manihot L.

The Hibiscus manihot L. (HML) Medic, an edible hibiscus of the Malvaceae family, is abundant with flavonoids. The study investigated how Rhizopus-arrhizus-31-assisted pretreatment affects the extraction and bioactivity of flavonoids from HML. The fiber structure of the fermented flavonoid sample (RFF) appears looser, more porous, and more disordered than the unfermented flavonoid sample (RUF). RFF demonstrates milder conditions and yields higher extraction rates. According to the Box-Behnken response surface optimization experiment, the optimal conditions for RFF include a material-liquid ratio of 1:41 g/mL, a 2 h extraction time, a 57% ethanol concentration, and an extraction temperature of 800 °C, resulting in a 3.69% extraction yield, which is 39.25% higher than that of RUF. Additionally, RFF exhibits greater activity than RUF in the radical-scavenging system. The IC50 values for DPPH, OH, and ABTS radicals are 83.43 µg/mL and 82.62 µg/mL, 208.38 µg/mL and 175.99 µg/mL, and 108.59 µg/mL and 75.39 µg/mL for RUF and RFF, respectively. UPLC-QTOF-MS analysis of the active components in the HML flavonoid sample revealed significant differences in the chromatograms of RUF and RFF, indicating that biofermentation led to substantial changes in composition and content from HML.

An Anti-CD7 Antibody-Drug Conjugate Target Showing Potent Antitumor Activity for T-Lymphoblastic Leukemia (T-ALL).

Acute T-lymphoblastic leukemia (T-ALL) is a type of leukemia that can occur in both pediatric and adult populations. Compared to acute B-cell lymphoblastic leukemia (B-ALL), patients with T-cell T-ALL have a poorer therapeutic efficacy. In this study, a novel anti-CD7 antibody-drug conjugate (ADC, J87-Dxd) was successfully generated and used for T-ALL treatment. Firstly, to obtain anti-CD7 mAbs, we expressed and purified the CD7 protein extracellular domain. Utilizing hybridoma technology, we obtained three anti-CD7 mAbs (J87, G73 and A15) with a high affinity for CD7. Both the results of immunofluorescence and Biacore assay indicated that J87 (KD = 1.54 × 10-10 M) had the highest affinity among the three anti-CD7 mAbs. In addition, an internalization assay showed the internalization level of J87 to be higher than that of the other two mAbs. Next, we successfully generated the anti-CD7 ADC (J87-Dxd) by conjugating DXd to J87 via a cleavable maleimide-GGFG peptide linker. J87-Dxd also possessed the ability to recognize and bind CD7. Using J87-Dxd to treat T-ALL cells (Jurkat and CCRF-CEM), we observed that J87-Dxd bound to CD7 was internalized into T-ALL cells. Moreover, J87-Dxd treatment significantly induced the apoptosis of Jurkat and CCRF-CEM cells. The IC50 (half-maximal inhibitory concentration) value of J87-Dxd against CCRF-CEM obtained by CCK-8 assay was 6.3 nM. Finally, to assess the antitumor efficacy of a J87-Dxd in vivo, we established T-ALL mouse models and treated mice with J87-Dxd or J87. The results showed that on day 24 after tumor inoculation, all mice treated with J87 or PBS died, whereas the survival rate of mice treated with J87-Dxd was 80%. H&E staining showed no significant organic changes in the heart, liver, spleen, lungs and kidneys of all mice. In summary, we demonstrated that the novel anti-CD7 ADC (J87-Dxd) had a potent and selective effect against CD7-expressing T-All cells both in vitro and in vivo, and could thus be expected to be further developed as a new drug for the treatment of T-ALL or other CD7-expression tumors.

Poster Session: Investigating temporal evolutions of perceptual choice within biological and artificial neural networks.

Perceptual decisions involve a process that evolves over time until it reaches a decision boundary. It's important to understand how this process unfolds. Recent psychophysical data indicates that the visual system extracts motion axis information faster than motion direction information (Kwon et al., 2015, J Vision). To understand the underlying mechanisms, we developed a biophysically realistic cortical network model of decision making. We generalized the two-variable reduced spiking neural network (Wong et al., 2006, J Neuroscience) to four-variable. The network input is based on motion energy (Adelson et al., 1985, Josa a) and the temporal profile of surround influence (Tadin et al., 2006, J Neuroscience). The model reproduces the prior experimental findings, showing the motion axis extraction before direction extraction. It reveals a stronger axis-wise inhibitory connection between the selective neural populations than the direction-wise inhibitory connection. We further designed a recurrent deep neural network to validate the neural population connectivity pattern. Our model provides a quantitative explanation for the temporal evolution of motion direction judgments. The results show that the spatiotemporal filtering for visual motion integration, the center-surround antagonism, and stronger axis-wise inhibitory connection between the selective neural populations can explain how the visual system can extract motion axis orientation before detecting motion direction.

ATP-citrate lyase controls endothelial gluco-lipogenic metabolism and vascular inflammation in sepsis-associated organ injury.

Sepsis involves endothelial cell (EC) dysfunction, which contributes to multiple organ failure. To improve therapeutic prospects, elucidating molecular mechanisms of vascular dysfunction is of the essence. ATP-citrate lyase (ACLY) directs glucose metabolic fluxes to de novo lipogenesis by generating acetyl-Co-enzyme A (acetyl-CoA), which facilitates transcriptional priming via protein acetylation. It is well illustrated that ACLY participates in promoting cancer metastasis and fatty liver diseases. Its biological functions in ECs during sepsis remain unclear. We found that plasma levels of ACLY were increased in septic patients and were positively correlated with interleukin (IL)-6, soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), and lactate levels. ACLY inhibition significantly ameliorated lipopolysaccharide challenge-induced EC proinflammatory response in vitro and organ injury in vivo. The metabolomic analysis revealed that ACLY blockade fostered ECs a quiescent status by reducing the levels of glycolytic and lipogenic metabolites. Mechanistically, ACLY promoted forkhead box O1 (FoxO1) and histone H3 acetylation, thereby increasing the transcription of c-Myc (MYC) to facilitate the expression of proinflammatory and gluco-lipogenic genes. Our findings revealed that ACLY promoted EC gluco-lipogenic metabolism and proinflammatory response through acetylation-mediated MYC transcription, suggesting ACLY as the potential therapeutic target for treating sepsis-associated EC dysfunction and organ injury.

Representational Geometries Reveal Differential Effects of Response Correlations on Population Codes in Neurophysiology and Functional Magnetic Resonance Imaging.

Two sensory neurons usually display trial-by-trial spike-count correlations given the repeated representations of a stimulus. The effects of such response correlations on population-level sensory coding have been the focal contention in computational neuroscience over the past few years. In the meantime, multivariate pattern analysis (MVPA) has become the leading analysis approach in functional magnetic resonance imaging (fMRI), but the effects of response correlations among voxel populations remain underexplored. Here, instead of conventional MVPA analysis, we calculate linear Fisher information of population responses in human visual cortex (five males, one female) and hypothetically remove response correlations between voxels. We found that voxelwise response correlations generally enhance stimulus information, a result standing in stark contrast to the detrimental effects of response correlations reported in empirical neurophysiological studies. By voxel-encoding modeling, we further show that these two seemingly opposite effects actually can coexist within the primate visual system. Furthermore, we use principal component analysis to decompose stimulus information in population responses onto different principal dimensions in a high-dimensional representational space. Interestingly, response correlations simultaneously reduce and enhance information on higher- and lower-variance principal dimensions, respectively. The relative strength of the two antagonistic effects within the same computational framework produces the apparent discrepancy in the effects of response correlations in neuronal and voxel populations. Our results suggest that multivariate fMRI data contain rich statistical structures that are directly related to sensory information representation, and the general computational framework to analyze neuronal and voxel population responses can be applied in many types of neural measurements.SIGNIFICANCE STATEMENT Despite the vast research interest in the effect of spike-count noise correlations on population codes in neurophysiology, it remains unclear how the response correlations between voxels influence MVPA in human imaging. We used an information-theoretic approach and showed that unlike the detrimental effects of response correlations reported in neurophysiology, voxelwise response correlations generally improve sensory coding. We conducted a series of in-depth analyses and demonstrated that neuronal and voxel response correlations can coexist within the visual system and share some common computational mechanisms. These results shed new light on how the population codes of sensory information can be evaluated via different neural measurements.

Synthesis and characterization of fucoidan/chitosan-coated nanoliposomes for enhanced stability and oral bioavailability of hydrophilic catechin and hydrophobic juglone.

This study aimed to improve the thermodynamic performance of nanoliposomes (NLs) using fucoidan (F) as the second-layer coating biopolymer along with chitosan (CS), to control the delivery and bioavailability of catechin (C) and juglone (J). The stabilized liposomal carrier of F/CS-conjugated JC-NL (F-CS-JC-NL) was developed with optimum concentrations of CS (0.09 wt%) and F (0.10 wt%), with the highest encapsulation efficiency of juglone (95.47%) and catechin (90.88%). Physicochemical characterization revealed that F-CS-JC-NL disclosed improved stability under different pH and ionic strengths, with the maximum juglone/catechin retention under thermal, oxidative and storage conditions. In vitro digestion revealed that NL double-coating (F-CS-JC-NL) significantly reduced compound leakage in the gastrointestinal tract, providing a controlled release and better bioavailability of juglone/catechin compared to CS-JC-NL and JC-NL. Conclusively, this study provides a novel NL-based delivery carrier with enhanced physicochemical stability and controlled release that might have promising use in delivering functional ingredients.

The rapid change in mental health among college students after introduction of on-campus quarantine during the 2022 Shanghai COVID-19 lockdown.

Objectives: Among the various impacts of disasters in terms of emotions, quarantine has been proven to result in significant increases in mental health problems. Studies of psychological resilience during outbreaks of epidemics tend to focus on long-term social quarantine. In contrast, insufficient studies have been conducted examining how rapidly negative mental health outcomes occur and how these outcomes change over time. We evaluated the time course of psychological resilience (over three different phases of quarantine) among students at Shanghai Jiao Tong University to investigate the influence of unexpected changes on college students. Methods: An online survey was conducted from 5 to 7 April 2022. A structured online questionnaire was administered using a retrospective cohort trial design. Before 9 March (Period 1), individuals engaged in their usual activities without restrictions. From 9 to 23 March (Period 2), the majority of students were asked to remain in their dormitories on campus. From 24 March to early April (Period 3), restrictions were relaxed, and students were gradually allowed to participate in essential activities on campus. We quantified dynamic changes in the severity of students' depressive symptoms over the course of these three periods. The survey consisted of five sets of self-reported questions: demographic information, lifestyle/activity restrictions, a brief mental health history, COVID-19-related background, and the Beck Depression Inventory, second edition. Results: A total of 274 college students aged 18-42 years (mean = 22.34; SE = 0.24) participated in the study (58.39% undergraduate students, 41.61% graduate students; 40.51% male, 59.49% female). The proportion of students with depressive symptoms was 9.1% in Period 1, 36.1% in Period 2, and 34.67% in Period 3. Depressive symptoms increased notably with the introduction of the quarantine in Periods 2 and 3. Lower satisfaction with the food supplied and a longer duration of physical exercise per day were found to be positively associated with changes in depression severity in Periods 2 and 3. Quarantine-related psychological distress was more evident in students who were in a romantic relationship than in students who were single. Conclusion: Depressive symptoms in university students rapidly increased after 2 weeks of quarantine and no perceptible reversal was observed over time. Concerning students in a relationship, ways to take physical exercise and to relax should be provided and the food supplied should be improved when young people are quarantined.

Assessment of vibration modulated regional cerebral blood flow with MRI.

Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.

A drug screening to identify novel combinatorial strategies for boosting cancer immunotherapy efficacy.

BACKGROUND: Chimeric antigen receptor (CAR) T cells and immune checkpoint blockades (ICBs) have made remarkable breakthroughs in cancer treatment, but the efficacy is still limited for solid tumors due to tumor antigen heterogeneity and the tumor immune microenvironment. The restrained treatment efficacy prompted us to seek new potential therapeutic methods. METHODS: In this study, we conducted a small molecule compound library screen in a human BC cell line to identify whether certain drugs contribute to CAR T cell killing. Signaling pathways of tumor cells and T cells affected by the screened drugs were predicted via RNA sequencing. Among them, the antitumor activities of JK184 in combination with CAR T cells or ICBs were evaluated in vitro and in vivo. RESULTS: We selected three small molecule drugs from a compound library, among which JK184 directly induces tumor cell apoptosis by inhibiting the Hedgehog signaling pathway, modulates B7-H3 CAR T cells to an effector memory phenotype, and promotes B7-H3 CAR T cells cytokine secretion in vitro. In addition, our data suggested that JK184 exerts antitumor activities and strongly synergizes with B7-H3 CAR T cells or ICBs in vivo. Mechanistically, JK184 enhances B7-H3 CAR T cells infiltrating in xenograft mouse models. Moreover, JK184 combined with ICB markedly reshaped the tumor immune microenvironment by increasing effector T cells infiltration and inflammation cytokine secretion, inhibiting the recruitment of MDSCs and the transition of M2-type macrophages in an immunocompetent mouse model. CONCLUSION: These data show that JK184 may be a potential adjutant in combination with CAR T cells or ICB therapy.

Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma.

A craniopharyngioma (CP) is a rare epithelial tumor of the sellar and parasellar region. CPs are difficult to treat due to their anatomical proximity to critical nervous structures, which limits the ability of the surgeon to completely resect the lesion, exposing patients to a high risk of recurrence. The treatment of craniopharyngiomas is primarily surgery and radiotherapy. So far, neither a cell line nor an animal model has been established, and thus data on other treatment options, such as chemotherapy and immunotherapy, are limited. Here, the expression profile of the pan-cancer antigen B7-H3 in various cancer types including CP was examined by immunohistochemistry. An in vitro organoid model was established by using fresh tissue biospecimens of CP. Based on the organoid model, we evaluated the antitumor efficacy of B7-H3-targeted immunotherapy on CP. As a result, the highest expression of B7-H3 was observed in CP tissues across various cancer types. Although B7-H3-targeted chimeric antigen-receptor T cells show obvious tumor-killing effects in the traditional 2D cell culture model, limited antitumor effects were observed in the 3D organoid model. The B7-H3-targeted antibody-DM1 conjugate exhibited a potent tumor suppression function both in 2D and 3D models. In conclusion, for the first time, we established an organoid model for CP and our results support that B7-H3 might serve as a promising target for antibody-drug conjugate therapy against craniopharyngioma.

Ultra-high field (10.5T) diffusion-weighted MRI of the macaque brain.

Diffu0sion-weighted magnetic resonance imaging (dMRI) is a non-invasive imaging technique that provides information about the barriers to the diffusion of water molecules in tissue. In the brain, this information can be used in several important ways, including to examine tissue abnormalities associated with brain disorders and to infer anatomical connectivity and the organization of white matter bundles through the use of tractography algorithms. However, dMRI also presents certain challenges. For example, historically, the biological validation of tractography models has shown only moderate correlations with anatomical connectivity as determined through invasive tract-tracing studies. Some of the factors contributing to such issues are low spatial resolution, low signal-to-noise ratios, and long scan times required for high-quality data, along with modeling challenges like complex fiber crossing patterns. Leveraging the capabilities provided by an ultra-high field scanner combined with denoising, we have acquired whole-brain, 0.58 mm isotropic resolution dMRI with a 2D-single shot echo planar imaging sequence on a 10.5 Tesla scanner in anesthetized macaques. These data produced high-quality tractograms and maps of scalar diffusion metrics in white matter. This work demonstrates the feasibility and motivation for in-vivo dMRI studies seeking to benefit from ultra-high fields.

Generation and characterization of nanobubbles in ionic liquid for a green extraction of polyphenols from Carya cathayensis Sarg.

Nanobubbles (NBs) generated-nanojets membrane poration have gained enormous attention. In this study, NBs were fabricated as a novel green approach to assist ionic liquid (IL) [C4C1im][BF4] extraction of polyphenols from Carya cathayensis Sarg. husk. NBs were successfully generated with mean size of 85.47 ± 5 nm, zeta potential of +39 ± 2.24 mV, and concentration of 21.15 ± 0.75 × 108 particles/mL (stable for over 48 h in IL solution). Compared to common solutions extract, IL-NBs extract showed significantly higher (p < 0.05) antioxidant activity and polyphenols yields with a total polyphenol, total flavonoid, and total tannins contents of 85.67 ± 2.05 mg GAE/g DW, 42.44 ± 1.17 mg CE/g DW, and 8.2 ± 0.05 mg TAE/g DW, respectively. The SEM results confirmed that NBs' nanojets caused morphological destruction of the husk powder. Overall, IL-NBs solution showed better extraction efficiency of polyphenols than other solutions, giving insight into a new "green" nanotechnology-based extraction method.

Atypically larger variability of resource allocation accounts for visual working memory deficits in schizophrenia.

Working memory (WM) deficits have been widely documented in schizophrenia (SZ), and almost all existing studies attributed the deficits to decreased capacity as compared to healthy control (HC) subjects. Recent developments in WM research suggest that other components, such as precision, also mediate behavioral performance. It remains unclear how different WM components jointly contribute to deficits in schizophrenia. We measured the performance of 60 SZ (31 females) and 61 HC (29 females) in a classical delay-estimation visual working memory (VWM) task and evaluated several influential computational models proposed in basic science of VWM to disentangle the effect of various memory components. We show that the model assuming variable precision (VP) across items and trials is the best model to explain the performance of both groups. According to the VP model, SZ exhibited abnormally larger variability of allocating memory resources rather than resources or capacity per se. Finally, individual differences in the resource allocation variability predicted variation of symptom severity in SZ, highlighting its functional relevance to schizophrenic pathology. This finding was further verified using distinct visual features and subject cohorts. These results provide an alternative view instead of the widely accepted decreased-capacity theory and highlight the key role of elevated resource allocation variability in generating atypical VWM behavior in schizophrenia. Our findings also shed new light on the utility of Bayesian observer models to characterize mechanisms of mental deficits in clinical neuroscience.

Action video game play facilitates "learning to learn".

Previous work has demonstrated that action video game training produces enhancements in a wide range of cognitive abilities. Here we evaluate a possible mechanism by which such breadth of enhancement could be attained: that action game training enhances learning rates in new tasks (i.e., "learning to learn"). In an initial controlled intervention study, we show that individuals who were trained on action video games subsequently exhibited faster learning in the two cognitive domains that we tested, perception and working memory, as compared to individuals who trained on non-action games. We further confirmed the causal effect of action video game play on learning ability in a pre-registered follow-up study that included a larger number of participants, blinding, and measurements of participant expectations. Together, this work highlights enhanced learning speed for novel tasks as a mechanism through which action video game interventions may broadly improve task performance in the cognitive domain.

Dissociable Neural Representations of Adversarially Perturbed Images in Convolutional Neural Networks and the Human Brain.

Despite the remarkable similarities between convolutional neural networks (CNN) and the human brain, CNNs still fall behind humans in many visual tasks, indicating that there still exist considerable differences between the two systems. Here, we leverage adversarial noise (AN) and adversarial interference (AI) images to quantify the consistency between neural representations and perceptual outcomes in the two systems. Humans can successfully recognize AI images as the same categories as their corresponding regular images but perceive AN images as meaningless noise. In contrast, CNNs can recognize AN images similar as corresponding regular images but classify AI images into wrong categories with surprisingly high confidence. We use functional magnetic resonance imaging to measure brain activity evoked by regular and adversarial images in the human brain, and compare it to the activity of artificial neurons in a prototypical CNN-AlexNet. In the human brain, we find that the representational similarity between regular and adversarial images largely echoes their perceptual similarity in all early visual areas. In AlexNet, however, the neural representations of adversarial images are inconsistent with network outputs in all intermediate processing layers, providing no neural foundations for the similarities at the perceptual level. Furthermore, we show that voxel-encoding models trained on regular images can successfully generalize to the neural responses to AI images but not AN images. These remarkable differences between the human brain and AlexNet in representation-perception association suggest that future CNNs should emulate both behavior and the internal neural presentations of the human brain.

Vigilance-Avoidance Toward Negative Faces in Social Anxiety With and Without Comorbid Depression.

Despite the growing evidence for the attentional bias toward emotional related stimuli in patients with social anxiety disorder (SAD), it remains unclear how the attentional bias manifests in normal individuals with SAD and/or depressive traits. To address this question, we recruited three groups of normal participants with different psychiatric traits-individuals with comorbid SAD and depression (SADd, N = 19), individuals with only SAD (SAD, N = 15), and healthy control individuals (HC, N = 19). In a dot-probe paradigm, participants view angry, disgusted, and sad face stimuli with durations ranging from very brief (i.e., 14ms) that renders stimuli completely intangible, to relatively long (i.e., 2000ms) that guarantees image visibility. We find significant early vigilance (i.e., on brief stimuli) and later avoidance (i.e., on long stimuli) toward angry faces in the SADd group. We also find vigilance toward angry and disgusted faces in the SAD group. To our best knowledge, this is the first study to unify both vigilance and avoidance within the same experimental paradigm, providing direct evidence for the "vigilance-avoidance" theory of comorbid SAD and depression. In sum, these results provide evidence for the potential behavioral differences induced by anxiety-depression comorbidity and a single trait in non-clinical populations, but the lack of a depression-only group cannot reveal the effects of high levels of depression on the results. The limitations are discussed.