Construction and application of H1R ligand screening materials based on SMA stabilization and his-tag covalent immobilization of membrane proteins.

The histamine H1 receptor (H1R) plays a pivotal role in allergy initiation and undergoes the necessity of devising a high-throughput screening approach centered on H1R to screen novel ligands effectively. This study suggests a method employing styrene maleic acid (SMA) extraction and His-tag covalent bonding to immobilize H1R membrane proteins, minimizing the interference of nonspecific proteins interference while preserving native protein structure and maximizing target exposure. This approach was utilized to develop a novel material for high-throughput ligand screening and implemented in cell membrane chromatography (CMC). An H1R-His-SMALPs/CMC model was established and its chromatographic performance (selectivity, specificity and lifespan) validated, demonstrating a significant enhancement in lifespan compared to previous CMC models. Subsequently, this model facilitated high-throughput screening of H1R ligands in the compound library and preliminary activity verification of potential H1R antagonists. Identification of a novel H1R antagonist laid the foundation for further development in this area.

Dorsomorphin attenuates ABCG2-mediated multidrug resistance in colorectal cancer.

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

Thymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers.

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2-•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2-• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

In Vivo Classification and Characterization of Carotid Atherosclerotic Lesions with Integrated 18F-FDG PET/MRI.

BACKGROUND: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. METHODS: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. RESULTS: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. CONCLUSIONS: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

Identification of WNK1 as a therapeutic target to suppress IgH/MYC expression in multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy demanding innovative therapeutic strategies. Targeting MYC, the notorious yet traditionally undruggable oncogene, presents an appealing avenue. Here, using a genome-scale CRISPR-Cas9 screen, we identify the WNK lysine-deficient protein kinase 1 (WNK1) as a regulator of MYC expression in MM cells. Genetic and pharmacological inhibition of WNK1 reduces MYC expression and, further, disrupts the MYC-dependent transcriptional program. Mechanistically, WNK1 inhibition attenuates the activity of the immunoglobulin heavy chain (IgH) enhancer, thus reducing MYC transcription when this locus is translocated near the MYC locus. WNK1 inhibition profoundly impacts MM cell behaviors, leading to growth inhibition, cell-cycle arrest, senescence, and apoptosis. Importantly, the WNK inhibitor WNK463 inhibits MM growth in primary patient samples as well as xenograft mouse models and exhibits synergistic effects with various anti-MM compounds. Collectively, our study uncovers WNK1 as a potential therapeutic target in MM.

Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

Targeted platelet with hydrogen peroxide responsive behavior for non-alcoholic steatohepatitis detection.

The most common chronic liver illness, non-alcoholic fatty liver disease (NAFLD), refers to a range of abnormalities of the liver with varying degrees of steatosis. When the clinical symptoms including liver damage, inflammation, and fibrosis, are added to the initial steatosis, NAFLD becomes non-alcoholic steatohepatitis (NASH), the problematic and severe stage. The diagnosis of NASH at the right time could therefore effectively prevent deterioration of the disease. Considering that platelets (PLTs) could migrate to the sites of inflamed liver sinusoids with oxidative stress during the development of NASH, we purified the PLTs from fresh blood and engineered their surface with hydrogen peroxide (H2O2) responsive fluorescent probe (5-DP) through lipid fusion. The engineered PLT-DPs were recruited and trapped in the inflammation foci of the liver with NASH through interaction with the extracellular matrix, including hyaluronan and Kupffer cells. Additionally, the fluorescence of 5-DP on the surface of PLT-DP was significantly enhanced upon reacting with the elevated level of H2O2 in the NASH liver. Thus, PLT-DP has great promise for NASH fluorescence imaging with high selectivity and sensitivity.

Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke.

OBJECTIVES: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS: Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS: Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS: The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.

Efficacy of partial and complete resuscitative endovascular balloon occlusion of the aorta in the hemorrhagic shock model of liver injury.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) can temporarily control traumatic bleeding. However, its prolonged use potentially leads to ischemia-reperfusion injury (IRI). Partial REBOA (pREBOA) can alleviate ischemic burden; however, its security and effectiveness prior to operative hemorrhage control remains unknown. Hence, we aimed to estimate the efficacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun. METHODS: Twenty Landrace pigs were randomized into control (no aortic occlusion) (n=5), intervention with complete REBOA (cREBOA) (n=5), continuous pREBOA (C-pREBOA) (n=5), and sequential pREBOA (S-pREBOA) (n=5) groups. In the cREBOA and C-pREBOA groups, the balloon was inflated for 60 min. The hemodynamic and laboratory values were compared at various observation time points. Tissue samples immediately after animal euthanasia from the myocardium, liver, kidneys, and duodenum were collected for histological assessment using hematoxylin and eosin staining. RESULTS: Compared with the control group, the survival rate of the REBOA groups was prominently improved (all P<0.05). The total volume of blood loss was markedly lower in the cREBOA group (493.14±127.31 mL) compared with other groups (P<0.01). The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups (P<0.05). At 120 min, the S-pREBOA group showed higher alanine aminotransferase (P<0.05) but lower blood urea nitrogen compared with the cREBOA group (P<0.05). CONCLUSION: In this trauma model with liver injury, a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure, despite persistent hemorrhage. Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures, and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.

Comparison of 18F-FDG PET and arterial spin labeling MRI in evaluating Alzheimer's disease and amnestic mild cognitive impairment using integrated PET/MR.

BACKGROUND: Developing biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR. RESULTS: Analyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR. CONCLUSION: ASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI.

Structural and functional changes in the brain after chronic complete thoracic spinal cord injury.

This study aimed to investigate whether brain anatomical structures and functional network connectivity are altered after chronic complete thoracic spinal cord injury (cctSCI) and to determine how these changes impact clinical outcomes. Structural and resting-state functional MRI was performed for 19 cctSCI patients (18 for final statistics) and 19 healthy controls. Voxel-based morphometry (VBM) was used to assess gray matter volume (GMV) with differences between cctSCI patients and controls. VBM results were used as seeds for whole-brain functional connectivity (FC) analysis. The relationship between brain changes and clinical variables was investigated. Compared with those of the control group, the left triangular inferior frontal gyrus, middle frontal gyrus, orbital inferior frontal gyrus, precuneus and parietal superior gyrus volumes of SCI patients decreased, while the left superior frontal gyrus and supplementary motor area volumes increased. Additionally, when the regions with increased GMV were used as seeds, the FC of the parahippocampus and thalamus increased. Subsequent partial correlation analysis showed a positive correlation between FC and total sensorimotor score based on the ASIA criteria (p = 0.001, r = 0.746). Overall, the structural and functional changes in the brain after cctSCI occurred in some visual and cognitive areas and sensory or motor control areas. These findings aid in improving our understanding of the underlying brain injury mechanisms and the subsequent structural and functional reorganization to reveal potential therapeutic targets and track treatment outcomes.

Multiparametric hippocampal signatures for early diagnosis of Alzheimer's disease using 18F-FDG PET/MRI Radiomics.

PURPOSE: This study aimed to explore the utility of hippocampal radiomics using multiparametric simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) for early diagnosis of Alzheimer's disease (AD). METHODS: A total of 53 healthy control (HC) participants, 55 patients with amnestic mild cognitive impairment (aMCI), and 51 patients with AD were included in this study. All participants accepted simultaneous PET/MRI scans, including 18F-fluorodeoxyglucose (18F-FDG) PET, 3D arterial spin labeling (ASL), and high-resolution T1-weighted imaging (3D T1WI). Radiomics features were extracted from the hippocampus region on those three modal images. Logistic regression models were trained to classify AD and HC, AD and aMCI, aMCI and HC respectively. The diagnostic performance and radiomics score (Rad-Score) of logistic regression models were evaluated from 5-fold cross-validation. RESULTS: The hippocampal radiomics features demonstrated favorable diagnostic performance, with the multimodal classifier outperforming the single-modal classifier in the binary classification of HC, aMCI, and AD. Using the multimodal classifier, we achieved an area under the receiver operating characteristic curve (AUC) of 0.98 and accuracy of 96.7% for classifying AD from HC, and an AUC of 0.86 and accuracy of 80.6% for classifying aMCI from HC. The value of Rad-Score differed significantly between the AD and HC (p < 0.001), aMCI and HC (p < 0.001) groups. Decision curve analysis showed superior clinical benefits of multimodal classifiers compared to neuropsychological tests. CONCLUSION: Multiparametric hippocampal radiomics using PET/MRI aids in the identification of early AD, and may provide a potential biomarker for clinical applications.

Dual decline in subjective gait speed and domain-specific cognition is associated with higher risk of incident dementia in older Japanese adults: A 15-year age-specific cohort study.

OBJECTIVES: Dual decline in gait speed and cognition has been found to have higher dementia risk than no decline or pure decline. However, evidence from the Asian population is lacking. Therefore, we aimed to investigate the association of dual decline from age 65 to 70 years with late-life dementia in older Japanese adults with different personal characteristics. METHODS: Data were collected from an age-specific cohort study conducted in 482 Japanese 65-year-old adults. We investigated participant demographics, medical histories, lifestyles, subjective gait speed, and cognition at both 64/65 and 70/71 years old, and confirmed dementia until age of 85 years. Cox proportion hazard models were used to estimate the risk of dementia, with adjustments for covariates, and death was treated as a competing risk. RESULTS: After a mean follow-up period of 12.5-years, 111 participants developed dementia. Older adults with dual decline are more likely to have hyperlipidemia, diabetes, and smoking habits. And we found that dual decline in gait speed and domain-specific cognition was associated with a higher risk of dementia compared with no decline in most cognitive tests, with the highest risk observed for gait speed combined with memory (sub-distribution hazard ratio:3.89, 95 %, confidence intervals: [1.68-9.01]). However, significant differences only existed in men after stratification by sex. CONCLUSIONS: A dual decline in subjective gait speed and cognition may serve as a robust predictor of dementia over a decade prior to its onset, particularly in men. These findings highlighted the importance of screening for dual decline at an early age.

Factors associated with COVID-19 misinformation rebuttal among college students: a descriptive study.

Background: The deluge of COVID-19 misinformation makes people confused, and acting on such misinformation can kill, leading to the tragic outcome of death. This makes it necessary to identify significant factors associated with college students' susceptibility. Objective: This descriptive study sought to ascertain factors significantly associated with college students' susceptibility to online COVID-19 misinformation. Methods: To assess college students' susceptibility to COVID-19 misinformation, we first chose as independent variables some demographic information, some well-developed, validated literacy tools, and the Patient Health Questionnaire-9 Items. Second, we selected as the dependent variable COVID-19 myths from some authoritative, official websites. Third, we integrated the independent and dependent variables into an online questionnaire. Fourth, we recruited students from Nantong University in China to participate in an online questionnaire survey. Finally, based on the data collected, we conducted quantitative and qualitative analyses to relate the independent variables to the dependent variable. Results: Five hundred forty-six students participated in the survey voluntarily, and all questionnaires they answered were valid. The participants had an average of 2.32 (SD = 0.99) years of higher education. They have a mean age of 20.44 (SD = 1.52) years. 434 (79.5%) of the 546 participants were females. The frequency of their Internet use averaged 3.91 (SD = 0.41), indicating that they logged onto the Internet almost every day. Their self-reported Internet skill was rated 3.79 (SD = 1.07), indicating that the participants rated their Internet skills as basically "good." The mean scores of the sub-constructs in the AAHLS were 6.14 (SD = 1.37) for functional health literacy, 5.10 (SD = 1.65) for communicative health literacy, and 11.13 (SD = 2.65) for critical health literacy. These mean scores indicated that the participants needed help to read health-related materials "sometimes," the frequency that they knew how to communicate effectively with professional health providers was between "often" and "sometimes," and the frequency that they were critical about health information was between "often" and "sometimes," respectively. The sum of their scores for eHealth literacy averaged 28.29 (SD = 5.31), showing that they had a relatively high eHealth literacy level. The mean score for each question in the GHNT was determined at 1.31 (SD = 0.46), 1.36 (SD = 0.48), 1.41 (SD = 0.49), 1.77 (SD = 0.42), 1.51 (SD = 0.50), and 1.54 (SD = 0.50), respectively. These mean scores showed that a high percentage of the participants answered the 6 questions wrongly, especially Questions 4-6. Similarly, participants performed unsatisfactorily in answering the 3 questions in the CRT, with a mean score of 1.75 (SD = 0.43), 1.55 (SD = 0.50), and 1.59 (SD = 0.49) for each question, respectively. In the PHQ-9, the participants reported that they never felt depressed or felt depressed only for 1-3 days in the past week. The mean score for myths 1-6 and 9-10 ranged from 1.15 (SD = 0.36) to 1.29 (SD = 0.46). This meant that the participants rated these myths false. However, most of the participants rated myths 7-8 true (1.54, SD = 0.50; 1.49, SD = 0.50), showing that they were highly susceptible to these 2 pieces of misinformation. Through data analysis via Logistic Regression (forward stepwise), we found that (1) at an average threshold of 0.5, Internet use frequency, functional health literacy, general health numeracy, reflective thinking tendency, and depression severity were significant predictors of susceptibility to misinformation for both male and female students, (2) at a higher threshold of 0.8, aggregated general health numeracy scores and functional health literacy scores, as well as depression severity were predictors of susceptibility to misinformation for both male and female students, (3) functional health literacy, general health literacy, and depression predicted resistance to misinformation for female students, and (4) internet use frequency and self-reported digital health literacy predicted resistance to misinformation for male students. Conclusion: We revealed the complexity, dynamics, and differences in age, gender, education, Internet exposure, communicative health literacy, and cognitive skills concerning college students' susceptibility to online COVID-19 misinformation. Hopefully, this study can provide valuable implications for counteracting COVID-19 misinformation among Chinese college students.

Impact of brain segmentation methods on regional metabolism quantification in 18F-FDG PET/MR analysis.

BACKGROUND: Accurate analysis of quantitative PET data plays a crucial role in studying small, specific brain structures. The integration of PET and MRI through an integrated PET/MR system presents an opportunity to leverage the benefits of precisely aligned structural MRI and molecular PET images in both spatial and temporal dimensions. However, in many clinical workflows, PET studies are often performed without the aid of individually matched structural MRI scans, primarily for the sake of convenience in the data collection and brain segmentation possesses. Currently, two commonly employed segmentation strategies for brain PET analysis are distinguished: methods with or without MRI registration and methods employing either atlas-based or individual-based algorithms. Moreover, the development of artificial intelligence (AI)-assisted methods for predicting brain segmentation holds promise but requires further validation of their efficiency and accuracy for clinical applications. This study aims to compare and evaluate the correlations, consistencies, and differences among the above-mentioned brain segmentation strategies in quantification of brain metabolism in 18F-FDG PET/MR analysis. RESULTS: Strong correlations were observed among all methods (r = 0.932 to 0.999, P < 0.001). The variances attributable to subject and brain region were higher than those caused by segmentation methods (P < 0.001). However, intraclass correlation coefficient (ICC)s between methods with or without MRI registration ranged from 0.924 to 0.975, while ICCs between methods with atlas- or individual-based algorithms ranged from 0.741 to 0.879. Brain regions exhibiting significant standardized uptake values (SUV) differences due to segmentation methods were the basal ganglia nuclei (maximum to 11.50 ± 4.67%), and various cerebral cortexes in temporal and occipital regions (maximum to 18.03 ± 5.52%). The AI-based method demonstrated high correlation (r = 0.998 and 0.999, P < 0.001) and ICC (0.998 and 0.997) with FreeSurfer, substantially reducing the time from 8.13 h to 57 s on per subject. CONCLUSIONS: Different segmentation methods may have impact on the calculation of brain metabolism in basal ganglia nuclei and specific cerebral cortexes. The AI-based approach offers improved efficiency and is recommended for its enhanced performance.

Using the Multidimensional Health Locus of Control Scale Form C to Investigate Health Beliefs About Bladder Cancer Prevention and Treatment Among Male Patients: Cross-Sectional Study.

BACKGROUND: Bladder cancer is a leading cause of death among Chinese male populations in recent years. The health locus of control construct can mediate health status and outcomes, and it has proven helpful in predicting and explaining specific health-related behaviors. However, it has never been used to investigate health beliefs about bladder cancer prevention and treatment. OBJECTIVE: This study aimed to classify male patients into different latent groups according to their beliefs about bladder cancer prevention and treatment and to identify associated factors to provide implications for the delivery of tailored education and interventions and the administration of targeted prevention and treatment. METHODS: First, we designed a four-section questionnaire to solicit data: section 1-age, gender, and education; section 2-the communicative subscale of the All Aspects of Health Literacy Scale; section 3-the eHealth Literacy Scale; and section 4-health beliefs about bladder cancer prevention and treatment measured by the Multidimensional Health Locus of Control Scale Form C. We hypothesized that the participants' health beliefs about bladder cancer prevention and treatment measured in section 4 could be closely associated with information collected through sections 1 to 3. We recruited 718 Chinese male patients from Qilu Hospital of Shandong University, China, and invited them to participate in a web-based questionnaire survey. Finally, we used latent class analysis to identify subgroups of men based on their categorical responses to the items on the Multidimensional Health Locus of Control Scale Form C and ascertained factors contributing to the low self-efficacy group identified. RESULTS: We identified 2 subgroups defined as low and moderate self-efficacy groups representing 75.8% (544/718) and 24.2% (174/718) of the total sample, respectively. Men in the low self-efficacy cluster (cluster 1: 544/718, 75.8%) were less likely to believe in their own capability or doctors' advice to achieve optimal outcomes in bladder cancer prevention and treatment. Men in the moderate self-efficacy cluster (cluster 2: 174/718, 24.2%) had distinct psychological traits. They had stronger beliefs in their own capability to manage their health with regard to bladder cancer prevention and treatment and moderate to high levels of trust in health and medical professionals and their advice to achieve better prevention and treatment outcomes. Four factors contributing to low self-efficacy were identified, including limited education (Year 6 to Year 12), aged ≥44 years, limited communicative health literacy, and limited digital health literacy. CONCLUSIONS: This was the first study investigating beliefs about bladder cancer prevention and treatment among Chinese male patients. Given that bladder cancer represents a leading cause of death among Chinese male populations in recent years, the low self-efficacy cluster and associated contributing factors identified in this study can provide implications for clinical practice, health education, medical research, and health policy-making.

Infiltrated IL-17A-producing gamma delta T cells play a protective role in sepsis-induced liver injury and are regulated by CCR6 and gut commensal microbes.

Introduction: Sepsis is a common but serious disease in intensive care units, which may induce multiple organ dysfunctions such as liver injury. Previous studies have demonstrated that gamma delta (γδ) T cells play a protective role in sepsis. However, the function and mechanism of γδ T cells in sepsis-induced liver injury have not been fully elucidated. IL-17A-producing γδ T cells are a newly identified cell subtype. Methods: We utilized IL-17A-deficient mice to investigate the role of IL-17A-producing γδ T cells in sepsis using the cecum ligation and puncture (CLP) model. Results: Our findings suggested that these cells were the major source of IL-17A and protected against sepsis-induced liver injury. Flow cytometry analysis revealed that these γδ T cells expressed Vγ4 TCR and migrated into liver from peripheral post CLP, in a CCR6-dependent manner. When CLP mice were treated with anti-CCR6 antibody to block CCR6-CCL20 axis, the recruitment of Vγ4+ γδ T cells was abolished, indicating a CCR6-dependent manner of migration. Interestingly, pseudo germ-free CLP mice treated with antibiotics showed that hepatic IL-17A+ γδ T cells were regulated by gut commensal microbes. E. coli alone were able to restore the protective effect in pseudo germ-free mice by rescuing hepatic IL-17A+ γδ T cell population. Conclusion: Our research has shown that Vγ4+ IL-17A+ γδ T cells infiltrating into the liver play a crucial role in protecting against sepsis-induced liver injury. This protection was contingent upon the recruitment of CCR6 and regulated by gut commensal microbes.

Effects of Near-Infrared Pulsed Light on the Attention of Human Beings Using Electroencephalography.

In our previous studies, photobiomodulation (PBM) stimulation can induce significant brain activation in normal subjects. In an open-eye study, the PBM stimulation was able to increase the power of alpha rhythms and theta waves, as well as decrease the beta activities after PBM stimulation. However, in the closed eyes study, the alpha rhythms in the laser group were reduced. This means the PBM stimulation can induce specific brainwaves under different conditions. Thus, to investigate the effects of PBM stimulation on human's attention, forty students were recruited in this single-blind randomized trial. A PBM stimulator, with seven pcs laser diodes (LDs), frequency 10 Hz, 30 mW/each LD, and wavelength 830 nm, was used to radiate the palm of the subject. PBM stimulation was found to induce significant variation in beta activity in most of the regions of the brain in the laser group. Compared to the placebo group, the PBM stimulation has a significant change in beta activity on electroencephalography (EEG). Three types of tests, the random number test, the Stroop color-word test, and the Multiple-Dimension Attention Test (MDAT), were used to evaluate the effects of the PBM stimulation. The scores of MDAT in the laser group increased more significantly than those in the placebo group after PBM stimulation (p < 0.01). An improvement in attention was observed in this study.

Lactobacillus paracasei subsp. paracasei X12 Strain Induces Apoptosis in HT-29 Cells through Activation of the Mitochondrial Pathway.

L. paracasei subsp. paracasei X12 was obtained from traditional cheese produced in northwestern China. In this study, we showed that whole peptidoglycan (WPG), extracted from L. paracasei subsp. paracasei X12, inhibited proliferation and induced apoptosis in HT-29 cells in a dose-dependent manner. In addition, WPG-induced apoptosis was associated with the loss of mitochondrial membrane potential (Ψm), the release of cytochrome c (Cyto-C) from mitochondrialto cytosolic spaces, activation of Caspase 3, and accumulation of intracellular reactive oxygen species (ROS). Finally, semi-quantitative RT-PCR showed that these events were accompanied by upregulation of proapoptotic genes (Bax or Bad) and downregulation of antiapoptotic genes (Bcl-xl). Taken together, our results demonstrated that WPG induced apoptosis in HT-29 cells through activation of the mitochondrial pathway. WPG exerted only minor toxicity upon noncancerous cells and therefore might be used as a natural agent in the treatment of cancer in future.

Site-Specific Covalent Immobilization of SMA-Stabilized ACE2 for SARS-CoV-2 Recognition and Drug Screening.

Membrane protein (MP)-based biomaterials have a wide range of applications in drug screening, antigen detection, and ligand-receptor interaction analysis. Traditional MP immobilization methods have the disadvantage of disordered protein immobilization orientation, leading to the shielded binding domain and unreliable binding pattern. Herein, we describe a site-specific covalent immobilization of MPs, which utilizes the styrene maleic acid (SMA) detergent-free extraction method of MPs as well as the covalent reaction between His-tag and divinyl sulfone (DVS). As an example, we covalently immobilized angiotensin-converting enzyme 2 (ACE2) on a cell membrane chromatography system (ACE2-His-SMALPs/CMC) in a site-specific manner and verified the specificity and stability of this system. This technique significantly improves the service life compared to the physisorption CMC column. The improved protein immobilization strategies of the ACE2-His-SMALPs/CMC system enable it to effectively recognize SARS-CoV-2 pseudoviral particles as well as detect viral particles in ambient air once combined with an aerosol collector; as a powerful ligand biosensor, the ACE2-His-SMALPs/CMC system was used to screen for compounds with anti-SARS-CoV-2 pseudovirus activity. In conclusion, the optimized MP immobilization strategy has been successfully applied to CMC technology, showing enhanced stability and sensitivity, which can provide an efficient and convenient membrane protein immobilization method for biomaterials.