SARS-CoV-2 not Detected in the Nasopharyngeal Sample but in Bronchoalveolar Lavage Fluid.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection typically relies on reverse transcription-polymerase chain reaction (RT-PCR) technology. However, there is a certain rate of missed detection of SARS-CoV-2 in nasopharyngeal samples, particularly among immunosuppressed individuals. METHODS: In this case, SARS-CoV-2 was detected in nasopharyngeal swabs and bronchoalveolar lavage fluid (BALF) using RT-PCR. Pulmonary imaging was performed using computed tomography (CT). Patient clinical data were retrieved from the Laboratory Information System (LIS). RESULTS: SARS-CoV-2 was negative in two nasopharyngeal tests of the patient, but was finally detected in BALF, confirming that the lung lesions were infected by SARS-CoV-2. CONCLUSIONS: In the post-epidemic era, it is necessary to use BALF to identify SARS-CoV-2 infection in cases where other factors have been ruled out in immunosuppressed individuals with pulmonary infections, especially when the nasopharyngeal test yields a negative result.

[An Intelligent Method for Optimizing Large-volume Medical Image Transmission].

In order to alleviate the conflict between medical supply and demand, and to improve the efficiency of medical image transmission, this study proposes an intelligent method for large-volume medical image transmission. This method extracts and generates keyword pairs by analyzing medical diagnostic reports, and uses a 3D-UNet to segment original image data into various sub-area based on its anatomy structure. Then, the sub-areas are scored through keyword pairs and preset scoring criteria, and transmitted to user frontend in the order of prioritization score. Experiments show that this method can fulfill physicians' requirements of radiology reading and diagnosis with only ten percent of data transmitted, which efficiently optimized traditional transmission procedures.

Expression of LINC00847 in Peripheral Blood Mononuclear Cells of Children with Asthma and Its Prediction between Asthma Exacerbation and Remission.

Objective: Asthma is defined as a heterogeneous disease that is usually characterized by chronic airway inflammation. Long noncoding RNAs play important roles in various biological processes including inflammation. To know more about the relationships between lncRNAs and asthma, we sought to the role of LINC00847 in peripheral blood mononuclear cells (PBMCs) of children with asthma exacerbation or asthma remission. Methods: Microarray analysis was performed on GSE143192 and GSE165934 datasets to screen differentially expressed lncRNAs (DElncRNAs) in human PBMCs between asthma patients and normal controls. LINC00847 was selected from DElncRNAs in human PBMCs between asthma patients and normal controls for further investigation. The expression levels of LINC00847 were quantified in PBMCs collected from 54 children with asthma exacerbation, 54 children with asthma remission, and 54 healthy children by real-time qPCR. The forced expiratory volume in the first second in percent predicted values (FEV1%), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), and peak expiratory flow rate (PEF%) were tested for evaluation of lung function. The concentration of immunoglobulin E (IgE) and eosinophil count was examined. The serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17A were determined by the ELISA method. Results: The expression level of LINC00847 in PBMCs of asthma exacerbation children was remarkably higher than that in PBMCs of asthma remission children and healthy children (p < 0.001); the expression level of LINC00847 in PBMCs of asthma remission children was notably higher than that in PBMCs of healthy children (p < 0.001). Pearson correlation analysis revealed that the expression levels of LINC00847 in PBMCs of asthma children were negatively correlated with FEV1% (r = -0.489), FEV1/FVC (r = -0.436), PEF% (r = -0.626), and IFN-γ level (r = -0.614) of asthma children, but positively correlated with IgE concentration (r = 0.680), eosinophil count (r = 0.780), IL-4 (r = 0.524), and IL-17A (r = 0.622) levels. When LINC00847 expression was used to distinguish asthma exacerbation from asthma remission, a 0.871 AUC (95% CI: 0.805-0.936) was yielded with sensitivity of 79.63% and specificity of 77.78%. Conclusion: The study demonstrates that increased LINC00847 expression may be associated with the development and progression of asthma, possibly serving as a novel biomarker for predicting asthma exacerbation from asthma remission.

Injectable Immunotherapeutic Thermogel for Enhanced Immunotherapy Post Tumor Radiofrequency Ablation.

Tumor radiofrequency ablation (RFA) is a local and minimally invasive application using high temperature to induce coagulative necrosis of tumor, which has been commonly used in clinic. Although the tumor fragments generated by RFA can activate the host's immune system, it may be insufficient to inhibit cancer recurrence due to many factors such as the inefficient antigen presentation by dendritic cells (DCs). In this research, a convenient local administration strategy by blocking rho-associated kinases (ROCK) is applied to amplify the immune responses triggered by RFA via promoting the phagocytosis capacity of DCs. Briefly, ROCK inhibitor, Y27632, is successfully dispersed in the amphiphilic copolymer poly(D,L-lactide-co-glycolide)-b-poly(ethyleneglycol)-b-poly(D,L-lactideco-glycolide) (PLGA-PEG-PLGA) solution, which is sol at room temperature and forms hydrogel quickly at body temperature, obviously prolonging the retention of Y27632 after injection. Interestingly, in the melanoma tumor model, the generated tumor fragments after RFA treatment are swallowed by DCs and undergo reinforced antigen presentation process with the help of gradual released Y27632, further effectively activating T cell mediated anti-tumor immune responses and significantly improving the therapeutic efficiency of RFA. Overall, such strategy remarkably prolongs the survival of mice after RFA treatment, showing great potential for clinical translation as an improvement strategy for RFA.

Preliminary investigation of the diagnostic value of shear wave elastography in evaluating the testicular spermatogenic function in patients with azoospermia.

To assess the diagnostic value of shear wave elastography (SWE) for evaluating the histological spermatogenic function of azoospermic males, 91 patients with azoospermia who underwent standardised greyscale ultrasound and SWE examinations followed by testicular biopsy were retrospectively recruited. Spermatogenic function was classified by biopsy as normal testicular spermatogenesis (n = 61), hypospermatogenesis (n = 18), spermatogenesis arrest (n = 6) and Sertoli cell-only syndrome (n = 6). Significant differences in testicular size and SWE values were observed between these 4 groups (p < .01). The mean SWE value had good discrimination power (AUC = 0.79) with a cut-off value of 1.55 KPa, a sensitivity of 0.58, specificity of 0.85, positive predictive value (PPV) of 0.36 and negative predictive value (NPV) of 0.93. Testicular volume had an AUC of 0.75. With a cut-off value of 8.41 ml, the testicular volume had a sensitivity of 0.58, specificity of 0.92, PPV of 0.54 and NPV of 0.93. The mean SWE value and testicular volume efficiently discriminated patients with normal spermatogenesis and hypospermatogenesis from patients with Sertoli cell-only syndrome and spermatogenesis arrest.

Effectiveness of social media-assisted course on learning self-efficacy.

The social media platform and the information dissemination revolution have changed the thinking, needs, and methods of students, bringing development opportunities and challenges to higher education. This paper introduces social media into the classroom and uses quantitative analysis to investigate the relation between design college students' learning self-efficacy and social media for design students, aiming to determine the effectiveness of social media platforms on self-efficacy. This study is conducted on university students in design media courses and is quasi-experimental, using a randomized pre-test and post-test control group design. The study participants are 73 second-year design undergraduates. Independent samples t-tests showed that the network interaction factors of social media had a significant impact on college students learning self-efficacy. The use of social media has a significant positive predictive effect on all dimensions of learning self-efficacy. Our analysis suggests that using the advantages and value of online social platforms, weakening the disadvantages of the network, scientifically using online learning resources, and combining traditional classrooms with the Internet can improve students' learning self-efficacy.

Exploring substrate-microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions.

Gut microbiota is an important modulator of human health and contributes to high inter-individual variation in response to food and pharmaceutical ingredients. The clinical outcomes of interventions with prebiotics, probiotics, and synbiotics have been mixed and often unpredictable, arguing for novel approaches for developing microbiome-targeted therapeutics. Here, we review how the gut microbiota determines the fate of and individual responses to dietary and xenobiotic compounds via its immense metabolic potential. We highlight that microbial metabolites play a crucial role as targetable mediators in the microbiota-host health relationship. With this in mind, we expand the concept of synbiotics beyond prebiotics' role in facilitating growth and engraftment of probiotics, by focusing on microbial metabolism as a vital mode of action thereof. Consequently, we discuss synbiotic compositions that enable the guided metabolism of dietary or co-formulated ingredients by specific microbes leading to target molecules with beneficial functions. A workflow to develop novel synbiotics is presented, including the selection of promising target metabolites (e.g. equol, urolithin A, spermidine, indole-3 derivatives), identification of suitable substrates and producer strains applying bioinformatic tools, gut models, and eventually human trials.In conclusion, we propose that discovering and enabling specific substrate-microbe interactions is a valuable strategy to rationally design synbiotics that could establish a new category of hybrid nutra-/pharmaceuticals.

(Poly)phenol-related gut metabotypes and human health: an update.

Dietary (poly)phenols have received great interest due to their potential role in the prevention and management of non-communicable diseases. In recent years, a high inter-individual variability in the biological response to (poly)phenols has been demonstrated, which could be related to the high variability in (poly)phenol gut microbial metabolism existing within individuals. An interplay between (poly)phenols and the gut microbiota exists, with (poly)phenols being metabolised by the gut microbiota and their metabolites modulating gut microbiota diversity and composition. A number of (poly)phenol metabolising phenotypes or metabotypes have been proposed, however, potential metabotypes for most (poly)phenols have not been investigated, and the relationship between metabotypes and human health remains ambiguous. This review presents updated knowledge on the reciprocal interaction between (poly)phenols and the gut microbiome, associated gut metabotypes, and subsequent impact on human health.

The Impact of Early-Life Cecal Microbiota Transplantation on Social Stress and Injurious Behaviors in Egg-Laying Chickens.

Injurious behaviors (i.e., aggressive pecking, feather pecking, and cannibalism) in laying hens are a critical issue facing the egg industry due to increased social stress and related health and welfare issues as well as economic losses. In humans, stress-induced dysbiosis increases gut permeability, releasing various neuroactive factors, causing neuroinflammation and related neuropsychiatric disorders via the microbiota-gut-brain axis, and consequently increasing the frequency and intensity of aggression and violent behaviors. Restoration of the imbalanced gut microbial composition has become a novel treatment strategy for mental illnesses, such as depression, anxiety, bipolar disorder, schizophrenia, impulsivity, and compulsivity. A similar function of modulating gut microbial composition following stress challenge may be present in egg-laying chickens. The avian cecum, as a multi-purpose organ, has the greatest bacterial biodiversity (bacterial diversity, richness, and species composition) along the gastrointestinal tract, with vitally important functions in maintaining physiological and behavioral homeostasis, especially during the periods of stress. To identify the effects of the gut microbiome on injurious behaviors in egg-laying chickens, we have designed and tested the effects of transferring cecal contents from two divergently selected inbred chicken lines on social stress and stress-related injurious behaviors in recipient chicks of a commercial layer strain. This article reports the outcomes from a multi-year study on the modification of gut microbiota composition to reduce injurious behaviors in egg-laying chickens. An important discovery of this corpus of experiments is that injurious behaviors in chickens can be reduced or inhibited through modifying the gut microbiota composition and brain serotonergic activities via the gut-brain axis, without donor-recipient genetic effects.

Improvement of olfactory function in AD mice mediated by immune responses under 40 Hz light flickering.

BACKGROUND: 40 Hz light flickering has shown promise as a non-invasive therapeutic approach for alleviating both pathological features and cognitive impairments in Alzheimer's disease (AD) model mice and AD patients. Additionally, vision may influence olfactory function through cross-modal sensory interactions. OBJECTIVE: To investigate the impact of 40 Hz light flickering on olfactory behavior in AD model mice and to explore the underlying mechanisms of this intervention. METHODS: We used immunofluorescence techniques to observe the activation of the olfactory bulb (OB) in C57BL/6J mice under 40 Hz light flickering. A buried food test was conducted to evaluate olfactory behavior in AD mice. Additionally, RNA sequencing technology was employed to detect transcriptional alterations in the OBs of AD mice following light stimulation. RESULTS: 40 Hz light flickering was found to effectively activate the OB. This stimulation led to enhanced olfactory behavior and did not alter P-tau protein mRNA levels within the OBs of AD mice. RNA sequencing revealed significant transcriptional changes in the OBs under flickering, particularly related to immune responses. CONCLUSION: Vision can influence olfactory function through cross-modal sensory interactions in rodent models. 40 Hz light stimulation improved olfactory performance in AD mice. However, the improvement in olfaction in AD mice is not related to changes in P-tau mRNA levels. Instead, it may be associated with an altered immune response, providing a scientific basis for the clinical treatment of olfactory disorders in Alzheimer's disease.

Blended knowledge sharing model in design professional.

Grounded in Nonaka and Takeuchi (Long Range Plan 54(4):102070, 2021) Socialization, Externalization, Combination, and Internalization (SECI) model, the present research develops a Blended Knowledge Sharing Activity (BKSA) model tailored for design practitioners, targeting the enhancement of learning outcomes and creativity. The investigation centers around the influence of BKSA on higher education students' learning achievements and creative potential, further delving into their application and performance relative to social media within design-related coursework. Employing a comprehensive methodological approach including sampling, t-tests, and structural equation modeling, questionnaires were disseminated to a cohort of 105 undergraduate students from two sophomore-level design classes. It is worth underscoring that despite the SECI model finding extensive applicability across numerous domains, its implementation within the context of design education remains comparatively underrepresented. This research lacuna served as a catalyst in our endeavor to apply the SECI model within knowledge-sharing activities specific to design majors, in anticipation of uncovering more potent strategies for learning and innovation. Our findings disclose a tangible positive correlation between BKSA and both the learning outcomes and creativity of undergraduate students. Moreover, the instrument we devised and utilized, acting as a robust measurement tool for the SECI model, provided additional validation for the beneficial influence of BKSA on university students' learning achievements and creative capacities. This novel insight not only redresses the underexplored application of the SECI model in design education but also furnishes a fresh theoretical vantage point for the amalgamation of blended learning and knowledge sharing paradigms.

Paper based SERS aptasensor towards dual-modal detection of interferon gamma.

Interferon gamma (IFN-γ), can serve as an active diagnostic biomarker of a broad spectrum of diseases such as auto inflammatory disease, viral and bacterial, parasites infections, and tumor control. The low physiological concentration of IFN-γ at pg‧mL-1 level for most diseases such as tuberculosis and lung cancer demand highly sensitive and selective detection methods. To achieve the goal, a novel paper-based SERS aptasensor towards rapid, dual-modal (visual and ultrasensitive) detection of IFN-γ is presented for the first time. A lateral flow platform with low-cost and user-friendly format in this study is adopted. The detection relies on the competition of the specific aptamer sequence of IFN-γ between its complementary DNA in the test line and IFN-γ in the sample solution. The presence of IFN-γ can be easily observed in the test line by naked eye and detected at pg‧mL-1 level by a portable Raman spectrometer. Linear detection range of 10-2000 pg‧mL-1 could be obtained with detection limit of 8.7 pg‧mL-1. In addition, as low as 10 pg/mL of IFN-γ in human serum could be detected, which is comparable with the results from ELISA.Clinical Relevance- This study establishes a simple, rapid, and low-cost assay for dual-modal detection of IFN-γ, which is in urgent demand in clinics especially vitally important in resource-limited areas.

Research Note: Probiotic, Bacillus subtilis, alleviates neuroinflammation in the hippocampus via the gut microbiota-brain axis in heat-stressed chickens.

High ambient temperature (heat stress, HS) is one of the critical environmental factors causing gut microbiota dysbiosis and increasing gut permeability, consequently inciting neuroinflammation in humans and various animals including chickens. The aim of this study was to examine if a probiotic, Bacillus subtilis, can reduce neuroinflammation in heat-stressed broiler chickens. Two hundred and forty 1-d-old broiler chicks were randomly assigned to 48 pens among 4 treatments in 2 identical, thermal-controlled rooms (n = 12): Thermoneutral (TN)-regular diet (RD), TN-PD (the regular diet mixed with a probiotic at 250 ppm), HS-RD, and HS-PD. The probiotic diet was fed from d 1, and HS at 32°C for 10-h daily was applied from d 15 for a 43-day trial. Results showed that compared to the TN broilers, the HS broilers had higher hippocampal interleukin (IL)-6, toll-like receptor (TLR)4, and heat shock protein (HSP)70 at both mRNA and protein levels regardless of dietary treatment (P < 0.05). In addition, the HS-PD broilers had higher levels of hippocampal IL-8 (P < 0.05) than the TN-PD broilers. Within the HS groups, compared to the HS-RD broilers, the HS-PD broilers had lower levels of IL-6, IL-8, HSP70, and TLR4 (P < 0.05) in the hippocampus. Within the TN groups, the TN-PD broilers had lower IL-8 at both mRNA expressions and protein levels (P < 0.05) but higher TLR4 protein levels (P < 0.05) in the hippocampus as compared to the TN-RD broilers. These results indicate that dietary supplementation of the Bacillus subtilis-based probiotic may reduce HS-induced brain inflammatory reactions in broilers via the gut-brain-immune axis. These results indicate the potential use of probiotics as a management strategy for reducing the impact of HS on poultry production.

Development of a novel (poly)phenol-rich diet score and its association with urinary (poly)phenol metabolites.

Background: Estimating (poly)phenol intake is challenging due to inadequate dietary assessment tools and limited food content data. Currently, a priori diet scores to characterise (poly)phenol-rich diets are lacking. This study aimed to develop a novel (poly)phenol-rich diet score (PPS) and explore its relationship with circulating (poly)phenol metabolites. Methods: A total of 543 healthy free-living participants aged 18-80 years completed a food frequency questionnaire (FFQ) (EPIC-Norfolk) and provided 24 h urine samples. The PPS was developed based on the relative intake (quintiles) of 20 selected (poly)phenol-rich food items abundant in the UK diet, including tea, coffee, red wine, whole grains, chocolate and cocoa products, berries, apples and juice, pears, grapes, plums, citrus fruits and juice, potatoes and carrots, onions, peppers, garlic, green vegetables, pulses, soy and soy products, nuts, and olive oil. Foods included in the PPS were chosen based on their (poly)phenol content, main sources of (poly)phenols, and consumption frequencies in the UK population. Associations between the PPS and urinary phenolic metabolites were investigated using linear models adjusting energy intake and multiple testing (FDR adjusted p < 0.05). Result: The total PPS ranged from 25 to 88, with a mean score of 54. A total of 51 individual urinary metabolites were significantly associated with the PPS, including 39 phenolic acids, 5 flavonoids, 3 lignans, 2 resveratrol and 2 other (poly)phenol metabolites. The total (poly)phenol intake derived from FFQs also showed a positive association with PPS (stdBeta 0.32, 95% CI (0.24, 0.40), p < 0.01). Significant positive associations were observed in 24 of 27 classes and subclasses of estimated (poly)phenol intake and PPS, with stdBeta values ranging from 0.12 (0.04, 0.20) for theaflavins/thearubigins to 0.43 (0.34, 0.51) for flavonols (p < 0.01). Conclusion: High adherence to the PPS diet is associated with (poly)phenol intake and urinary biomarkers, indicating the utility of the PPS to characterise diets rich in (poly)phenols at a population level.

Cecal microbiota transplantation: unique influence of cecal microbiota from divergently selected inbred donor lines on cecal microbial profile, serotonergic activity, and aggressive behavior of recipient chickens.

BACKGROUND: Accumulating evidence from human trials and rodent studies has indicated that modulation of gut microbiota affects host physiological homeostasis and behavioral characteristics. Similarly, alterations in gut microbiota could be a feasible strategy for reducing aggressive behavior and improving health in chickens. The study was conducted to determine the effects of early-life cecal microbiota transplantation (CMT) on cecal microbial composition, brain serotonergic activity, and aggressive behavior of recipient chickens. METHODS: Chicken lines 63 and 72 with nonaggressive and aggressive behavior, respectively, were used as donors and a commercial strain Dekalb XL was used as recipients for CMT. Eighty-four 1-d-old male chicks were randomly assigned to 1 of 3 treatments with 7 cages per treatment and 4 chickens per cage (n = 7): saline (control, CTRL), cecal solution of line 63 (63-CMT), and cecal solution of line 72 (72-CMT). Transplantation was conducted via oral gavage once daily from d 1 to 10, and then boosted once weekly from week 3 to 5. At weeks 5 and 16, home-cage behavior was recorded, and chickens with similar body weights were assigned to paired aggression tests between the treatments. Samples of blood, brain, and cecal content were collected from the post-tested chickens to detect CMT-induced biological and microbiota changes. RESULTS: 63-CMT chickens displayed less aggressive behavior with a higher hypothalamic serotonergic activity at week 5. Correspondingly, two amplicon sequence variants (ASVs) belonging to Lachnospiraceae and one Ruminococcaceae UCG-005 ASV were positively correlated with the levels of brain tryptophan and serotonin, respectively. 72-CMT chickens had lower levels of brain norepinephrine and dopamine at week 5 with higher levels of plasma serotonin and tryptophan at week 16. ASVs belonging to Mollicutes RF39 and GCA-900066225 in 72-CMT chickens were negatively correlated with the brain 5-hydroxyindoleacetic acid (5-HIAA) at week 5, and one Bacteroides ASV was negatively correlated with plasma serotonin at week 16. CONCLUSION: Results indicate that CMT at an early age could regulate aggressive behavior via modulating the cecal microbial composition, together with central serotonergic and catecholaminergic systems in recipient chickens. The selected CMT could be a novel strategy for reducing aggressive behavior through regulating signaling along the microbiota-gut-brain axis.

Mutational profiling of Chinese patients with thyroid cancer.

Background: The incidence of thyroid cancer in China has rapidly increased in recent decades. As the genetic profiles of thyroid cancer vary dramatically between different geographical regions, a comprehensive genetic landscape of thyroid cancer in the Chinese population is urgently needed. Methods: We retrospectively included thyroid cancer patients from three Chinese medical centers between February 2015 and August 2020. To dissect the genomic profiling of these patients, we performed targeted next-generation sequencing on their tumor tissues using a 1,021-gene panel. Results: A total of 458 Chinese patients with thyroid cancer were enrolled, including four malignant histological subtypes arising from follicular epithelial thyroid cells. BRAF driver mutations were identified in 76.0% of patients, followed by RET rearrangements (7.6%) and RAS driver mutations (4.1%). Tumors with more somatic mutations correlated with worse clinical characteristics, including older age at diagnosis, less differentiation of tumor, larger tumor size, lymph node metastasis and distal metastasis. Subclonal BRAF mutations occurred in 20% (6/30) of patients and were frequent in poorly differentiated or anaplastic tumors (33.3% [2/6] vs. 4.2% [1/24], P = 0.09) and those with distal metastasis (50.0% [2/4] vs. 8.7% [2/23], P = 0.09). Tumors with TERT promoter mutations had significantly more somatic mutations (average: 6.5 vs. 1.8, P < 0.001). Moreover, TERT promoter mutations were not associated with lymph node metastasis but significantly associated with older age at diagnosis and poorly differentiated or anaplastic tumors, regardless of their clonal architecture. Conclusion: Our results shed light on the molecular pathogenesis and clinical characteristics of thyroid cancer in the Chinese population. The number of somatic mutations, TERT promoter mutations, and the clonal architecture of BRAF mutations should be considered in the risk stratification of thyroid cancer.

An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy.

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.

Sensory gamma entrainment: Impact on amyloid protein and therapeutic mechanism.

The deposition of amyloid ß peptide (Aß) is one of the main pathological features of AD. The much-talked sensory gamma entrainment may be a new treatment for Aß load. Here we reviewed the generation and clearance pathways of Aß, aberrant gamma oscillation in AD, and the therapeutic effect of sensory gamma entrainment on AD. In addition, we discuss these results based on stimulus parameters and possible potential mechanisms. This provides the support for sensory gamma entrainment targeting Aß to improve AD.

Magnetic Resonance Imaging Nanoprobe Quantifies Nitric Oxide for Evaluating M1/M2 Macrophage Polarization and Prognosis of Cancer Treatments.

Macrophages play a crucial role in immune activation and provide great value in the prognosis of cancer treatments. Current strategies for prognostic evaluation of macrophages mainly target the specific biomarkers to reveal the number and distribution of macrophages in the tumors, whereas the phenotypic change of M1 and M2 macrophages in situ is less understood. Here, we designed an ultrasmall superparamagnetic iron oxide nanoparticle-based molecular imaging nanoprobe to quantify the repolarization of M2 to M1 macrophages by magnetic resonance imaging (MRI) using the redox-active nitric oxide (NO) as a vivid chemical target. The nanoprobe equipped with O-phenylenediamine groups could react with the intracellular NO molecules during the repolarization of M2 macrophages to the M1 phenotype, leading to electrical attraction and colloidal aggregation of the nanoprobes. Consequently, the prominent changes of the T1 and T2 relaxation in MRI allow for the quantification of the macrophage polarization. In a 4T1 breast cancer model, the MRI nanoprobe was able to reveal macrophage polarization and predict treatment efficiency in both immunotherapy and radiotherapy paradigms. This study presents a noninvasive approach to monitor the phenotypic changes of M2 to M1 macrophages in the tumors, providing insight into the prognostic evaluation of cancer treatments regarding macrophage-mediated immune responses.

Interplay between the (Poly)phenol Metabolome, Gut Microbiome, and Cardiovascular Health in Women: A Cross-Sectional Study from the TwinsUK Cohort.

BACKGROUND: Dietary (poly)phenol consumption is inversely associated with cardiovascular disease (CVD) risk in epidemiological studies, but little is known about the role of the gut microbiome in this relationship. METHODS: In 200 healthy females, aged 62.0 ± 10.0 years, from the TwinsUK cohort, 114 individual (poly)phenol metabolites were measured from spot urine using ultra-high-performance liquid chromatography-mass spectrometry. The associations between metabolites, the gut microbiome (alpha diversity and genera), and cardiovascular scores were investigated using linear mixed models adjusting age, BMI, fibre, energy intake, family relatedness, and multiple testing (FDR < 0.1). RESULTS: Significant associations were found between phenolic acid metabolites, CVD risk, and the gut microbiome. A total of 35 phenolic acid metabolites were associated with the Firmicutes phylum, while 5 metabolites were associated with alpha diversity (FDR-adjusted p < 0.05). Negative associations were observed between the atherosclerotic CVD (ASCVD) risk score and five phenolic acid metabolites, two tyrosol metabolites, and daidzein with stdBeta (95% (CI)) ranging from -0.05 (-0.09, -0.01) for 3-(2,4-dihydroxyphenyl)propanoic acid to -0.04 (-0.08, -0.003) for 2-hydroxycinnamic acid (FDR-adjusted p < 0.1). The genus 5-7N15 in the Bacteroidetes phylum was positively associated with the same metabolites, including 3-(3,5-dihydroxyphenyl)propanoic acid, 3-(2,4-dihydroxyphenyl)propanoic acid, 3-(3,4-dihydroxyphenyl)propanoic acid), 3-hydroxyphenylethanol-4-sulfate, and 4-hydroxyphenylethanol-3-sulfate)(stdBeta (95% CI): 0.23 (0.09, 0.36) to 0.28 (0.15, 0.42), FDR-adjusted p < 0.05), and negatively associated with the ASCVD score (stdBeta (95% CI): -0.05 (-0.09, -0.01), FDR-adjusted p = 0.02). Mediation analysis showed that genus 5-7N15 mediated 23.8% of the total effect of 3-(3,4-dihydroxyphenyl)propanoic acid on the ASCVD score. CONCLUSIONS: Coffee, tea, red wine, and several vegetables and fruits, especially berries, are the most abundant food sources of phenolic acids that have the strongest associations with CVD risk. We found that the gut microbiome, particularly the genus 5-7N15, partially mediates the negative association between urinary (poly)phenols and cardiovascular risk, supporting a key role of the gut microbiome in the health benefits of dietary (poly)phenols.