A cross-scenario and cross-subject domain adaptation method for driving fatigue detection.

OBJECTIVE: The scarcity of electroencephalogram (EEG) data, coupled with individual and scenario variations, leads to considerable challenges in real-world EEG-based driver fatigue detection. We propose a domain adaptation method that utilizes EEG data collected from a laboratory to supplement real-world EEG data and constructs a cross-scenario and cross-subject driver fatigue detection model for real-world scenarios. Approach. First, we collect EEG data from subjects participating in a driving experiment conducted in both laboratory and real-world scenarios. To address the issue of data scarcity, we build a real-world fatigued driving detection model by integrating the real-world data with the laboratory data. Then, we propose a method named cross-scenario and cross-subject domain adaptation (CS2DA), which aims to eliminate the domain shift problem caused by individual variances and scenario differences. Adversarial learning is adopted to extract the common features observed across different subjects within the same scenario. The multikernel maximum mean discrepancy method is applied to further minimize scenario differences. Additionally, we propose a conditional multikernel maximum mean discrepancy constraint to better utilize label information. Finally, we use seven rules to fuse the predicted labels. Main results. We evaluate the CS2DA method through extensive experiments conducted on the two EEG datasets created in this work: the SEED-VLA and the SEED-VRW datasets. Different domain adaptation methods are used to construct a real-world fatigued driving detection model using data from laboratory and real-world scenarios, as well as a combination of both. Our findings show that the proposed CS2DA method outperforms the existing traditional and adversarial learning-based domain adaptation approaches. We also find that combining data from both laboratory and real-world scenarios improves the performance of the model. Significance. This study contributes two EEG-based fatigue driving datasets and demonstrates that the proposed CS2DA method can effectively enhance the performance of a real-world fatigued driving detection model.

Psychological resilience and related factors among primary care workers in Wuhan, China: A cross-sectional study.

Purpose: Primary medical workers constitute a high-risk group for mental health problems, and psychological resilience might protect them from the negative psychological impacts of their work. Therefore, this study aimed to investigate the current situation of psychological resilience among primary care workers in Wuhan, China, as well as related factors. Methods: In this cross-sectional study, a total of 417 primary care workers (30.0 % men; 38.5 ± 8.5 years old) were randomly selected to complete a questionnaire. The brief version of the National Mental Health Literacy Questionnaire and the Psychological Resilience Scale were used to assess participants' mental health literacy and psychological resilience, respectively. Multiple linear regression was performed to identify factors associated with the psychological resilience of primary care workers. Results: More than four-fifths of the primary care workers included in this study exhibited appropriate levels of mental health knowledge. In terms of mental health skills, participants' attainment rates, ranging from high to low, were 60.9 % for distracting attention, 45.3 % for interpersonal support and 43.9 % for cognitive reappraisal. The average psychological resilience score obtained by primary care workers was 27.81 ± 5.71, and the factors associated with increased psychological resilience included being male, being older, and possessing higher mental health skills, including skills pertaining to interpersonal support and distracting attention. Conclusion: The psychological resilience of primary care workers in Wuhan is at a moderate level and thus requires further improvement. Although these medical staff exhibit appropriate levels of mental health knowledge, their mental health skills are relatively poor, despite the fact that interpersonal support and distracting attention are significantly associated with psychological resilience. Hence, interventions targeting mental health skills are recommended to promote psychological resilience among primary care workers.

Hyperactivation of SREBP induces Pannexin-1-dependent lytic cell death.

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.

LMNB1/CDKN1A Signaling Regulates the Cell Cycle and Promotes Hepatocellular Carcinoma Progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world. Lamin B1 (LMNB1) is a key component of the nuclear skeleton structure. Recent studies have found that LMNB1 is overexpressed in tumor tissues and is associated with the prognosis of patients. However, the underlying mechanism remains unclear in HCC. OBJECTIVE: This study aims to explore the clinical significance and molecular mechanisms of LMNB1 in HCC. METHODS: The expression level of LMNB1 and its clinical values were analyzed with public databases, and the level of LMNB1 in HCC tissues and adjacent normal tissues was confirmed by qRT-PCR and IHC. Functional assays were conducted to explore the impact of LMNB1 knockdown on cell proliferation both in vivo and in vitro. Additionally, Genes and Genomes enrichment analysis, recovery analysis, and ChIP assays were employed to investigate its underlying molecular mechanisms. Finally, we carried out an analysis of the relationship between LMNB1 and immune cell infiltration in HCC. RESULTS: LMNB1 was found to be overexpressed in HCC and correlated with the pathological stage and unfavorable prognosis. Functional assays demonstrated that LMNB1 promotes HCC proliferation both in vitro and in vivo. Further analysis revealed that LMNB1 promotes the progression of HCC by regulating CDKN1A expression. Furthermore, the infiltration of immune cells in HCC tissues suggests a potential correlation between immune infiltration cell markers and the expression of LMNB1. CONCLUSIONS: LMNB1 emerged as a promising therapeutic target and prognostic biomarker for HCC, with its expression showing a correlation with several immune infiltration cell markers.

A Predictive Model Based on the FBXO Family Reveals the Significance of Cyclin F in Hepatocellular Carcinoma.

OBJECTIVE: The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy. METHODS: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F (CCNF) through in vitro experiments. RESULTS: A predictive model involving three genes (CCNF, FBXO43, and FBXO45) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of CCNF in HCC cell lines reduced cell proliferation in vitro, suggesting that CCNF may be a potential therapeutic target for HCC. CONCLUSIONS: The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, CCNF is a potential therapeutic target for HCC.

Photocatalytic Nitrogen Fixation Coupled with the Generation of Value-Added Chemicals from N2 and Cellulose over MoO3 Nanosheets.

Photocatalytic nitrogen fixation from N2 provides an alternative strategy for ammonia (NH3) production, but it was limited by the consumption of a sacrificial electron donor for the currently reported half-reaction system. Here, we use naturally abundant and renewable cellulose as the sacrificial reagent for photocatalytic nitrogen fixation over oxygen-vacancy-modified MoO3 nanosheets as the photocatalyst. In this smartly designed photocatalytic system, the photooxidation of cellulose not only generates value-added chemicals but also provides electrons for the N2 reduction reaction and results in the production of NH3 with a maximum rate of 68 µmol·h-1·g-1. Also, the oxygen vacancies provide efficient active sites for both cellulose oxygenolysis and nitrogen fixation reactions. This work represents useful inspiration for realizing nitrogen fixation coupled with the generation of value-added chemicals from N2 and cellulose through a photocatalysis strategy.

Structural characteristics and antioxidant activities of a novel polysaccharide from Euphorbia himalayensis root.

Euphorbia himalayensis Boiss. is an alpine member of the Euphorbiaceae family. Its dried roots have been used to treat digestive problems and chest congestion in traditional Tibetan and Mongolian medicine. Despite thousands of years of use in medicine, the bioactive compounds of the root remain unknown. Herein, we isolated a novel aqueous-soluble polysaccharide (EHP2) from the E. himalayensis root and determined its structural characteristics via high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectrometry. The homogeneous molecular weight of EHP2 was 23.6 kDa with narrow polydisperity (Mw/Mn = 1.4), and EHP2 mainly comprised of glucose (86.4%), galactose (11.9%) and mannose (1.7%). The major backbone of EHP2 was →4)-α-D-GalAp-(1 â†’ 4)-α-D-Glcp-(1 â†’ and the branch chain was α-D-Glcp-(1→. The antioxidant activity of the EHP2 was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging assays, and antioxidant enzyme activity (SOD, GSH and MDA) was determined in human umbilical vein endothelial cells (HUVECs). The EHP2 demonstrated lower potential scavenging effects on DPPH and superoxide free radical scavenger than ascorbic acid, and in HUVECs, it led to increased SOD and GSH activities and decreased MDA levels. This study is the first to describe an E. himalayensis polysaccharide compound with potential antioxidant activity.

Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating Jmjd3.

Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1), both macrophages treated with statins in vitro or isolated from statin-treated mice in vivo, express lower levels pro-inflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

Efficacy and acceptability of music therapy for post-traumatic stress disorder: a systematic review and meta-analysis of randomized controlled trials.

Background: Music therapy is increasingly examined in randomized controlled trials (RCTs) and shows potential in treating post-traumatic stress disorder (PTSD).Objective: This systematic review and meta-analysis critically evaluates the current clinical evidence supporting the efficacy and acceptability of music therapy for PTSD.Method: RCTs comparing music therapy in addition to care as usual (CAU) versus either CAU alone or CAU combined with standard psychotherapy/pharmacotherapy for PTSD were retrieved from major English - and Chinese-language databases. Standardized mean differences (SMDs) for post-treatment PTSD symptom scores and risk differences (RDs) for retention rates upon treatment completion were calculated to assess the efficacy and acceptability of music therapy, respectively. The Cochrane risk of bias (RoB) tool 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) were used to assess the RoB of included studies and certainty of the evidence, respectively.Results: Nine studies, incorporating 527 PTSD patients, were included, all with high RoB. The post-treatment PTSD symptom scores were significantly lower in the music therapy group than the inactive control group (SMD = -1.64, P < .001), but comparable between the music therapy group and the active control group (SMD = -0.28, P = .330). The retention rates did not differ significantly between the music therapy group and both control groups (RD = 0.03, P = .769; RD = 0.16, P = .829). The GRADE rated certainty level of evidence as low.Conclusions: Although meta-analytic findings suggest that music therapy is effective in reducing post-traumatic symptoms in individuals with PTSD, with its therapeutic effect comparable to that of standard psychotherapy, the low level of certainty limits its generalizability. More methodologically stringent studies are warranted to strengthen the clinical evidence for the efficacy and acceptability of music therapy for PTSD.

This systematic review critically appraised the existing methodologically rigorous evidence for the efficacy and acceptability of music therapy for post-traumatic stress disorder (PTSD).The post-treatment PTSD symptom scores were significantly lower in the music therapy group than the inactive control group and comparable between the music therapy group and the active control group.The post-treatment retention rates did not differ significantly between the music therapy group and both the inactive and active control groups.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

Prevalence of prolonged grief disorder and its symptoms among bereaved individuals in China: a systematic review and meta-analysis.

Background: The prevalence of prolonged grief disorder (PGD) and its symptoms among the bereaved population in China vary considerably. Aims: This meta-analysis aims to estimate the prevalence of PGD and its symptoms among bereaved individuals in China. Methods: We conducted a literature search in major Chinese and English databases from their inception to 4 October 2023, for cross-sectional studies on the prevalence of PGD or its symptoms in bereaved Chinese individuals. The risk of bias of the included studies and certainty of the evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data ('JBI checklist') and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE), respectively. The 'metaprop' package in R V.4.1.2 was used to synthesise the prevalence. Results: A total of 28 studies involving 10 994 bereaved individuals were included in the analysis, with JBI checklist scores between 3 and 7. The combined prevalence (95% confidence interval) of PGD and its symptoms was 8.9% (4.2% to 17.6%) and 32.4% (18.2% to 50.8%), respectively. PGD and its symptoms were most prevalent among those who had lost their only child (22.7%) and those bereaved by earthquakes (80.4%), respectively. The GRADE system assigned a very low certainty level to the evidence for the pooled prevalence of PGD and its symptoms. Conclusions: The pooled prevalence of PGD and its symptoms indicate a potential high need for grief counselling services among bereaved individuals in China. This need is particularly pronounced in those who have lost their only child and those bereaved due to earthquakes. Further methodologically rigorous studies are needed to provide more accurate prevalence estimates. PROSPERO registration number: CRD42023432553.

Fatty acid-binding proteins 3, 7, and 8 bind cholesterol and facilitate its egress from lysosomes.

Cholesterol from low-density lipoprotein (LDL) can be transported to many organelle membranes by non-vesicular mechanisms involving sterol transfer proteins (STPs). Fatty acid-binding protein (FABP) 7 was identified in our previous study searching for new regulators of intracellular cholesterol trafficking. Whether FABP7 is a bona fide STP remains unknown. Here, we found that FABP7 deficiency resulted in the accumulation of LDL-derived cholesterol in lysosomes and reduced cholesterol levels on the plasma membrane. A crystal structure of human FABP7 protein in complex with cholesterol was resolved at 2.7 Å resolution. In vitro, FABP7 efficiently transported the cholesterol analog dehydroergosterol between the liposomes. Further, the silencing of FABP3 and 8, which belong to the same family as FABP7, caused robust cholesterol accumulation in lysosomes. These two FABP proteins could transport dehydroergosterol in vitro as well. Collectively, our results suggest that FABP3, 7, and 8 are a new class of STPs mediating cholesterol egress from lysosomes.

Intraoperative femurofibular angle combined with tibiofibular angle measurement has fewer correction errors in open-wedge high tibial osteotomy.

AIM: This study aimed to verify the accuracy of intraoperative femurofibular angle combined with tibiofibular angle (FFA-TFA) measurement and compare it with traditional alignment line methods in open-wedge high tibial osteotomy (OWHTO). METHODS: A total of 174 knees of 122 patients undergoing OWHTO and using an alignment line or FFA-TFA measurement as an index of optimal correction were included in this retrospective study. The intraoperative alignment line passed through the targeted weight-bearing line (WBL) of the tibial plateau in the alignment line group. The intraoperative FFA-TFA aligned to the preplanned FFA-TFA angle in the FFA-TFA group. WBL, FFA, TFA, and knee joint-line convergence angle of the femur and tibia were assessed as radiological results preoperatively and one year after surgery. The Knee Society Score and the Western Ontario and McMaster Universities were assessed as objective clinical results. RESULTS: Postoperative WBL in the FFA-TFA group was closer to the target WBL than in the alignment line group (FFA-TFA vs alignment line group: 1.43 ± 1.20% vs 3.82 ± 3.29%; P < 0.001). The FFA-TFA group had fewer over-correction and under-correction rates than the alignment line group (28.7% and 12.6% vs 11.5% and 3.40%; P < 0.001). No significant differences were observed in the clinical results between the two groups one year after surgery (P > 0.05). CONCLUSIONS: The intraoperative measurement of FFA-TFA had fewer complications in terms of under-correction and over-correction compared with the alignment line measurement. No significant differences between the two methods were observed in clinical results one year after surgery.

Modulating band structure through introducing Cu0/CuxO composites for the improved visible light driven ammonia synthesis.

The photocatalytic performance of ceria-based materials can be tuned by adjusting the surface structures with decorating the transition-metal, which are considered as the important active sites. Herein, cuprous oxide-metallic copper composite-doped ceria nanorods were assembled through a simple hydrothermal reduction method. The photocatalytic ammonia synthesis rates exhibit an inverted "V-shaped" trend with increasing Cu0/CuxO mole ratio. The best ammonia production rate, approximately 900 or 521 µmol·gcal-1·h-1 under full-spectra or visible light, can be achieved when the Cu0/CuxO ratio is approximately 0.16, and this value is 8 times greater than that of the original sample. The absorption edge of the as-prepared samples shifted towards visible wavelengths, and they also had appropriate ammonia synthesis levels. This research provides a strategy for designing noble metal-free photocatalysts through introducing the metal/metallic oxide compositesto the catalysts.

Elevated levels of loneliness in migrant children compared to nonmigrant children in urban China: a systematic review and meta-analysis of comparative studies.

PURPOSE OF REVIEW: About one in four children in China is a migrant child. This population has a higher risk of experiencing loneliness. However, existing studies present conflicting findings regarding the levels of loneliness among migrant children as compared to local urban children in urban China. This review performs a meta-analysis of studies comparing loneliness levels between these two groups. RECENT FINDINGS: A literature search of major Chinese- and English-language databases revealed 27 eligible comparative studies. These studies reported the means and standardized deviations of loneliness scores for both migrant and nonmigrant children in urban China. Meta-analysis results showed that migrant children experienced significantly higher levels of loneliness than their urban nonmigrant counterparts [standardized mean difference (SMD) = 0.21, P  < 0.001]. Subgroup analysis revealed that studies enrolling migrant children from migrant children's schools had significantly higher pooled SMDs than those enrolling children from public schools (0.346 vs. 0.120, P  = 0.047). SUMMARY: Migrant children in urban China experience higher levels of loneliness compared to their local urban peers. Efforts to create a socially inclusive, migrant-friendly environment and reduce social isolation among migrant children are crucial to help alleviate their feelings of loneliness.

Shaping immune landscape of colorectal cancer by cholesterol metabolites.

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.

Flexibility Retained: Unimpaired Updating of Expectations in Schizophrenia.

Flexibly and actively updating expectations based on feedback is crucial for navigating daily life. Previous research has shown that people with schizophrenia (PSZ) have difficulty adjusting their expectations. However, there are studies suggesting otherwise. To explore this further, we used a novel trial-based expectation updating paradigm called attribute amnesia. In the task, the participants needed to report the location of a target stimulus among distractors in pre-surprise trials. In the surprise trial, they were unexpectedly asked to report the identity of the target before reporting its location. Afterward, control trials were conducted whereby the participants were asked the same questions as in the surprise trial. Notably, the surprise trial and control trials were nearly identical, except that the participants expected to be asked about identity information in the control trials but not in the surprise trial. Thus, an improvement in identity reporting accuracy in the control trials in comparison with the surprise trial indicated active updating of expectations. In the current study, a total of 63 PSZ and 60 healthy control subjects (HCS) were enrolled. We found that both the PSZ and the HCS were unable to report information that they had fully attended to (i.e., identity) in the surprise trial. However, both groups showed a significant improvement in reporting identity information even in the first control trial. Critically, there was no significant difference in the magnitude of improvement between the two groups. The current findings indicate that PSZ have the ability to update their expectations as quickly and flexibly as HCS, at least in the context of the current task. The possible factors that might contribute to the discrepancy regarding expectation updating are discussed.

Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating JMJD3.

Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1), both macrophages treated with statins in vitro or isolated from statin-treated mice in vivo, express lower levels pro-inflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

Investigating Emotion EEG Patterns for Depression Detection with Attentive Simple Graph Convolutional Network.

Depression severely limits daily functioning, diminishes quality of life and possibly leads to self-harm and suicide. Noninvasive electroencephalography (EEG) has been shown effective as biomarkers for objective depression diagnose and treatment response prediction, and dry EEG electrodes further extend its availability for clinical use. Even though many efforts have been made to identify depression biomarkers, searching reliable EEG biomarkers for depression detection remains challenging. This work presents a systematic investigation of capabilities of emotion EEG patterns for depression detection using a dry EEG electrode system. We design an emotion elicitation paradigm with happy, neutral and sad emotions and collect EEG signals during film watching from 33 depressed patients and 40 healthy controls. The mean activation levels at frontal and temporal sites in the alpha, beta and gamma bands of the depressed group are different to those of the healthy group, indicating the impacts of depressive symptoms on the emotion experiences. To leverage the topology information among EEG channels for emotion recognition and depression detection, an Attentive Simple Graph Convolutional network is built. The deep depression-health classifier achieves a sensitivity of 81.93% and a specificity of 91.69% on the happy emotions, suggesting the promising use of the emotion neural patterns for distinguishing the depressed patients from the healthy controls.