NK cell transfer overcomes resistance to PD-(L)1 therapy in aged mice.

BACKGROUND: Cancer is the leading cause of death among older adults. Although the integration of immunotherapy has revolutionized the therapeutic landscape of cancer, the complex interactions between age and immunotherapy efficacy remain incompletely defined. Here, we aimed to elucidate the relationship between aging and immunotherapy resistance. METHODS: Flow cytometry was performed to evaluate the infiltration of immune cells in the tumor microenvironment (TME). In vivo T cell proliferation, cytotoxicity and migration assays were performed to evaluate the antitumor capacity of tumor antigen-specific CD8+ T cells in mice. Real-time quantitative PCR (qPCR) was used to investigate the expression of IFN-γ-associated gene and natural killer (NK)-associated chemokine. Adoptive NK cell transfer was adopted to evaluate the effects of NK cells from young mice in overcoming the immunotherapy resistance of aged mice. RESULTS: We found that elderly patients with advanced non-small cell lung cancer (aNSCLC) aged ≥ 75 years exhibited poorer progression-free survival (PFS), overall survival (OS) and a lower clinical response rate after immunotherapy. Mechanistically, we showed that the infiltration of NK cells was significantly reduced in aged mice compared to younger mice. Furthermore, the aged NK cells could also suppress the activation of tumor antigen-specific CD8+ T cells by inhibiting the recruitment and activation of CD103+ dendritic cells (DCs). Adoptive transfer of NK cells from young mice to aged mice promoted TME remodeling, and reversed immunotherapy resistance. CONCLUSION: Our findings revealed the decreased sensitivity of elderly patients to immunotherapy, as well as in aged mice. This may be attributed to the reduction of NK cells in aged mice, which inhibits CD103+ DCs recruitment and its CD86 expression and ultimately leads to immunotherapy resistance.

Quantitative MR imaging biomarkers for distinguishing inflammatory pancreatic mass and pancreatic cancer-a systematic review and meta-analysis.

OBJECTIVES: To evaluate the diagnostic performance of quantitative magnetic resonance (MR) imaging biomarkers in distinguishing between inflammatory pancreatic masses (IPM) and pancreatic cancer (PC). METHODS: A literature search was conducted using PubMed, Embase, the Cochrane Library, and Web of Science through August 2023. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the risk of bias and applicability of the studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated using the DerSimonian-Laird method. Univariate meta-regression analysis was used to identify the potential factors of heterogeneity. RESULTS: Twenty-four studies were included in this meta-analysis. The two main types of IPM, mass-forming pancreatitis (MFP) and autoimmune pancreatitis (AIP), differ in their apparent diffusion coefficient (ADC) values. Compared with PC, the ADC value was higher in MFP but lower in AIP. The pooled sensitivity/specificity of ADC were 0.80/0.85 for distinguishing MFP from PC and 0.82/0.84 for distinguishing AIP from PC. The pooled sensitivity/specificity for the maximal diameter of the upstream main pancreatic duct (dMPD) was 0.86/0.74, with a cutoff of dMPD ≤ 4 mm, and 0.97/0.52, with a cutoff of dMPD ≤ 5 mm. The pooled sensitivity/specificity for perfusion fraction (f) was 0.82/0.68, and 0.82/0.77 for mass stiffness values. CONCLUSIONS: Quantitative MR imaging biomarkers are useful in distinguishing between IPM and PC. ADC values differ between MFP and AIP, and they should be separated for consideration in future studies. CLINICAL RELEVANCE STATEMENT: Quantitative MR parameters could serve as non-invasive imaging biomarkers for differentiating malignant pancreatic neoplasms from inflammatory masses of the pancreas, and hence help to avoid unnecessary surgery. KEY POINTS: • Several quantitative MR imaging biomarkers performed well in differential diagnosis between inflammatory pancreatic mass and pancreatic cancer. • The ADC value could discern pancreatic cancer from mass-forming pancreatitis or autoimmune pancreatitis, if the two inflammatory mass types are not combined. • The diameter of main pancreatic duct had the highest specificity for differentiating autoimmune pancreatitis from pancreatic cancer.

Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review.

Background and Objective: Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease. Methods: For this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors". Key Content and Findings: Classical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC. Conclusions: Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

In Situ Electrochemical Rapid Induction of Highly Active γ-NiOOH Species for Industrial Anion Exchange Membrane Water Electrolyzer.

Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step (*O→*OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm-2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm-2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy.

Hepatic Sirt6 activation abrogates acute liver failure.

Acute liver failure (ALF) is a deadly illness due to insufficient detoxification in liver induced by drugs, toxins, and other etiologies, and the effective treatment for ALF is very limited. Among the drug-induced ALF, acetaminophen (APAP) overdose is the most common cause. However, the molecular mechanisms underlying APAP hepatoxicity remain incompletely understood. Sirtuin 6 (Sirt6) is a stress responsive protein deacetylase and plays an important role in regulation of DNA repair, genomic stability, oxidative stress, and inflammation. Here, we report that genetic and pharmacological activation of Sirt6 protects against ALF in mice. We first observed that Sirt6 expression was significantly reduced in the liver tissues of human patients with ALF and mice treated with an overdose of APAP. Then we developed an inducible Sirt6 transgenic mice for Cre-mediated overexpression of the human Sirt6 gene in systemic (Sirt6-Tg) and hepatic-specific (Sirt6-HepTg) manners. Both Sirt6-Tg mice and Sirt6-HepTg mice exhibited the significant protection against APAP hepatoxicity. In contrast, hepatic-specific Sirt6 knockout mice exaggerated APAP-induced liver damages. Mechanistically, Sirt6 attenuated APAP-induced hepatocyte necrosis and apoptosis through downregulation of oxidative stress, inflammation, the stress-activated kinase JNK activation, and apoptotic caspase activation. Moreover, Sirt6 negatively modulated the level and activity of poly (ADP-ribose) polymerase 1 (PARP1) in APAP-treated mouse liver tissues. Importantly, the specific Sirt6 activator MDL-800 exhibited better therapeutic potential for APAP hepatoxicity than the current drug acetylcysteine. Furthermore, in the model of bile duct ligation induced ALF, hepatic Sirt6-KO exacerbated, but Sirt6-HepTg mitigated liver damage. Collectively, our results demonstrate that Sirt6 protects against ALF and suggest that targeting Sirt6 activation could be a new therapeutic strategy to alleviate ALF.

Cold EMR vs. Hot EMR for the removal of sessile serrated polyps larger than 10 mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.

Machine learning unveils immune-related signature in multicenter glioma studies.

In glioma molecular subtyping, existing biomarkers are limited, prompting the development of new ones. We present a multicenter study-derived consensus immune-related and prognostic gene signature (CIPS) using an optimal risk score model and 101 algorithms. CIPS, an independent risk factor, showed stable and powerful predictive performance for overall and progression-free survival, surpassing traditional clinical variables. The risk score correlated significantly with the immune microenvironment, indicating potential sensitivity to immunotherapy. High-risk groups exhibited distinct chemotherapy drug sensitivity. Seven signature genes, including IGFBP2 and TNFRSF12A, were validated by qRT-PCR, with higher expression in tumors and prognostic relevance. TNFRSF12A, upregulated in GBM, demonstrated inhibitory effects on glioma cell proliferation, migration, and invasion. CIPS emerges as a robust tool for enhancing individual glioma patient outcomes, while IGFBP2 and TNFRSF12A pose as promising tumor markers and therapeutic targets.

Ni, Co-Embedded MOF-Derived N-Doped Bimetallic Porous Carbon for Adsorption-Photocatalytic Degradation of Organic Dyes and Antibiotics.

An efficient protocol for photocatalytic degradation of organic dyes and antibiotics has been successfully established via MOF-derived (MOF = metal-organic framework) Ni, Co-embedded N-doped bimetallic porous carbon nanocomposites (NiCo/NC). Such a NiCo/NC nanocomposite features well-distributed structures, suitable specific surface areas, and more active sites determined by various characterization analyses. The catalyst exhibits higher photocatalytic performance and stability toward the liquid-phase degradation of methylene blue (MB) under visible light irradiation for 60 min, after the adsorption-desorption equilibrium and the thorough degradation into H2O and CO2. Radical quenching experiments further confirmed the dominant effect of electron holes h+ and superoxide radical anions ·O2- for the MB photodegradation process. NiCo/NC was also appropriate for the degradation of Rhodamine B, methyl orange, tetracycline hydrochloride, and norfloxacin. Moreover, NiCo/NC is robust, and its photocatalytic activity is basically maintained after 8 cycles. This work is expected to provide additional information for the design of MOF-derived carbon material with more excellent properties and lay the foundation for further industrial applications.

Application of magnetic resonance imaging radiomics in endometrial cancer: a systematic review and meta-analysis.

PURPOSE: We aimed to systematically assess the methodological quality and clinical potential application of published magnetic resonance imaging (MRI)-based radiomics studies about endometrial cancer (EC). METHODS: Studies of EC radiomics analyses published between 1 January 2000 and 19 March 2023 were extracted, and their methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses and separate meta-analyses of studies exploring differential diagnoses and risk prediction were also performed. RESULTS: Forty-five studies involving 3 aims were included. The mean RQS was 13.77 (range: 9-22.5); publication bias was observed in the areas of 'index test' and 'flow and timing'. A high RQS was significantly associated with therapy selection-aimed studies, low QUADAS-2 risk, recent publication year, and high-performance metrics. Raw data from 6 differential diagnosis and 34 risk prediction models were subjected to meta-analysis, revealing diagnostic odds ratios of 23.81 (95% confidence interval [CI] 8.48-66.83) and 18.23 (95% CI 13.68-24.29), respectively. CONCLUSION: The methodological quality of radiomics studies involving patients with EC is unsatisfactory. However, MRI-based radiomics analyses showed promising utility in terms of differential diagnosis and risk prediction.

Setting the Theater for Creativity: Proposal for Integrating Temporal and Spatial Artificial Mnemonics as a Qualitative Artificial Development of the Autobiographical Naturalistic Mnemonics (AM).

Mnemonics are not only tools that empower memory but also have a significant role in qualitatively transforming mental functions and, hence, consciousness in general. A specific type of mnemonics is autobiographical mnemonics (AM) constructed of spatial, temporal, and semantic dimensions used in a naturalist form by individuals about their own experiences. This paper proposes a spatial-temporal mnemonic that transforms AM from a naturalist level into an artificial one. We consider allowing the intellect and consciousness to grasp the abstract flow of time in the global context of geography will contribute to setting the stage for creativity. By explicitly representing the abstract time-space theater, the intellect (the world view) is more able to reflect the abstract laws of reality (the world), hence, to make the intellect sphere objectively equipped to externalize the emerged meanings (the internalized reality) that reflect the internal content of experience and, hence, make sense of them as a crucial function in creative activity. The paper is a theoretical and methodological step for the empirical part of the proposal when the mnemonic should be used as a training tool to empower creativity factors.

Network pharmacology and in vivo evidence of the pharmacological mechanism of geniposide in the treatment of atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is a fundamental pathological state in various cardiovascular diseases. Geniposide, which is the main active component of Gardenia jasminides, is effective against AS. However, the underlying molecular mechanisms remain unclear. Here, we sought to elucidate them. METHODS: The targets of AS and geniposide were collected from online public databases. The potential mechanism of Geniposide in treating AS was predicted by constructing a protein-protein interaction (PPI) network and conducting Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses. Hub proteins and core pathways were verified by molecular docking and in vivo experiments. Moreover, the effect of geniposide on AS was assessed by measuring the atherosclerotic plaque area in the thoracic aorta of mice. ApoE-/- mice were used to establish AS models and randomly divided into different groups. Two different doses of geniposide were administered to the mice. Hematoxylin and eosin (HE) staining was performed to evaluate the effects of geniposide on AS. Oil Red O and Sirius Red staining were used to evaluate plaque stability. The protein expression of key markers involved in the signalling pathways was examined using western blotting and immunofluorescence. RESULTS: A total of 239 active targets, 3418 AS-related disease targets, and 129 overlapping targets were identified. Hub genes were detected, and molecular docking revealed that geniposide strongly interacted with hub proteins (AKT1, VEGFA, CTNNB1, MMP9, and EGFR). Moreover, 109 signalling pathways, including the Rap1 signalling pathway, were identified using enrichment analysis. The results of in vivo experiments demonstrated that geniposide reduced body weight and blood lipid levels, alleviated the formation of atherosclerotic plaques, enhanced plaque stability, and inhibited inflammation, at least partially, by activating the Rap1/PI3K/Akt signalling pathway in ApoE-/- mice. CONCLUSION: Geniposide can alleviate AS and enhance the stability of atherosclerotic plaques by regulating the Rap1/PI3K/Akt signalling pathway.

Relationship between phthalates exposure, risk of decreased ovarian reserve, and oxidative stress levels.

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study.

Between Meanings and Senses-Making Spaces: Agency and Ownership Emergence Formalization from Cultural-Historical Activity Theory Position, for an AI-Friendly Model.

Sense of agency and sense of ownership are considered crucial in autonomous systems. However, drawbacks still exist regarding how to represent their causal origin and internal structure, either in formalized psychological models or in artificial systems. This paper considers that these drawbacks are based on the ontological and epistemological duality in mainstream psychology and AI. By shedding light on the cultural-historical activity theory (CHAT) and dialectical logic, and by building on and extending related work, this paper attempts to investigate how the noted duality affects investigating the self and "I". And by differentiating between the space of meanings and the sense-making space, the paper introduces CHAT's position of the causal emergence of agency and ownership by stressing the twofold transition theory being central to CHAT. Furthermore, a qualitative formalized model is introduced to represent the emergence of agency and ownership through the emergence of the contradictions-based meaning with potential employment in AI.

Transcriptome and Hormonal Analysis of Agaricus bisporus Basidiome Response to Hypomyces perniciosus Infection.

Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. A. bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield because of malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation caused by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathological, physiological, and transcriptomic analyses. Results showed that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the metabolism level of phytohormones (N6-isopentenyladenosine, cis-zeatin, and N6-[delta 2-isopentenyl]-adenine) of the host's fruiting bodies rather than using toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.

Sexual orientation disparities in the prevalence of suicidal ideation among U.S adults aged 20 to 59 years: Results from NHANES 2005-2016.

Existing studies have been limited in providing nationally representative data on the relationship between sexual orientation and suicidal ideation (SI) among adults in the U.S. particularly in terms of gender and racial differences. To fill this research gap, we conducted a study using data from the NHANES conducted between 2005 and 2016. Survey-weighted logistic regression models were used to investigate the relationship between sexual orientation and SI risk. Additionally, we performed further analysis by stratifying the data based on demographic variables and performed sensitivity analysis to ensure the reliability of our findings. This study included a weighted sample of 16,564 adults, representing a noninstitutionalized U.S population of 840.1 million. The overall age-adjusted prevalence of SI was found to be 3.5 %. After adjusting for relevant covariates, the study revealed that individuals who identified as something else, homosexual, and bisexual had a higher prevalence risk of suicidal ideation (SI) compared to heterosexual participants. Additionally, the study found that heterosexual participants were 74.4 % less likely to experience SI compared to bisexual individuals. These findings highlight the urgent requirement for inclusive and supportive prevention strategies to effectively address SI among adult sexual minorities in the U.S.

SIRT6 Protects Against Lipopolysaccharide-Induced Inflammation in Human Pulmonary Lung Microvascular Endothelial Cells.

Inflammatory response in the pulmonary endothelium drives the pathogenesis of acute lung injury and sepsis. Sirtuin 6 (SIRT6), a member of class III NAD+-dependent deacetylases belonging to the sirtuin family, regulates senescence, metabolism, and inflammation and extends lifespan in mice and model organisms. However, the role of SIRT6 in pulmonary endothelial inflammation is unknown. Thus, we hypothesized that SIRT6 suppresses inflammatory response in human lung microvascular cells (HLMEC) and ensues monocyte adhesion to endothelial cells. Primary HLMECs were treated with control or SIRT6 adenovirus or SIRT6 agonist, with or without lipopolysaccharide (LPS) treatment. We observed that treatment with LPS did not affect the protein expression of SIRT6 in HLMECs. However, adenovirus-mediated SIRT6 overexpression attenuated LPS-induced VCAM1 gene and protein expression, followed by decreased monocyte adhesion to endothelial cells. Similarly, activation of SIRT6 by a recently reported SIRT6 activator UBCS039, but not the regioisomer negative control compound UBCS060, ameliorated LPS-induced VCAM1 mRNA and protein expression as well as monocyte adhesion. Moreover, luciferase assay revealed that SIRT6 adenovirus decreased the activity of NF-κB, the master regulator of vascular inflammation. Taken together, these results indicate that molecular and pharmacological activation of SIRT6 protects against lung microvascular inflammation via suppressing NF-κB activation, implicating the therapeutic potential of the SIRT6 activators for lung disorders associated with microvascular inflammation.

Ginsenoside F2-Mediated Intestinal Microbiota and Its Metabolite Propionic Acid Positively Impact the Gut-Skin Axis in Atopic Dermatitis Mice.

Atopic dermatitis (AD) is a complex inflammatory skin disease induced by multiple factors. AD can also cause intestinal inflammation and disorders of the gut microbiota. Ginseng is a kind of edible and medicinal plant; its main active components are ginsenosides. Ginsenosides have a variety of anti-inflammatory effects and regulate the gut microbiota; however, their role in AD and the underlying mechanisms are unclear. In this study, we found that intragastric administration of ginsenoside F2 improved AD-like skin symptoms and reduced inflammatory cell infiltration, serum immunoglobulin E levels, and mRNA expression of inflammatory cytokines in AD mice. 16s rRNA sequencing analysis showed that ginsenoside F2 altered the intestinal microbiota structure and enriched the short-chain fatty acid-producing microbiota in AD mice. Metabolomic analysis revealed that ginsenoside F2 significantly increased the propionic acid (Pa) content of feces and serum in AD mice, which was positively correlated with significant enrichment of Parabacteroides goldsteinii and Lactobacillus plantarum in the intestines. Pa inhibits inflammatory responses in the gut and skin of AD mice through the G-protein-coupled receptor43/NF-κB pathway, thereby improving skin AD symptoms. These results revealed, for the first time, the mechanism by which ginsenoside F2 improves AD through the Pa (a metabolite of intestinal microbiota)-gut-skin axis.

Deep learning reconstruction improves the image quality of low-dose temporal bone CT with otitis media and mastoiditis patients.

Objective: To evaluate the image quality of low-dose temporal bone computed tomography (CT) in otitis media and mastoiditis patients by using deep learning reconstruction (DLR). Materials and methods: A total of ninety-seven temporal bones from 53 consecutive adult patients who had suspected otitis media and mastoiditis and underwent temporal bone CT were prospectively enrolled. All patients underwent high resolution CT protocol (group A) and an additional low-dose protocol (group B). In group A, high resolution data were reconstructed by filter back projection (FBP). In group B, low-dose data were reconstructed by DLR mild (B1), DLR standard (B2) and DLR strong (B3). The objective image quality was analyzed by measuring the CT value and image noise on the transverse image and calculating the signal-to-noise ratio (SNR) on incudomallear joint, retroauricular muscle, vestibule and subcutaneous fat. Subjective image quality was analyzed by using a five-point scale to evaluate nine anatomical structures of middle and inner ear. The number of temporal bone lesions which involved in five structures of middle ear were assessed in group A, B1, B2 and B3 images. Results: There were no significant differences in the CT values of the four reconstruction methods at four structures (all p > 0.05). The DLR group B1, B2 and B3 had significantly less image noise and a significantly higher SNR than group A at four structures (all p < 0.001). The group B1 had comparable subjective image quality as group A in nine structures (all p > 0.05), however, the group B3 had lower subjective image quality than group A in modiolus, spiral osseous lamina and stapes (all p < 0.001), the group B2 had lower subjective image quality than group A in modiolus and spiral osseous lamina (both p < 0.05). The number of temporal bone lesions which involved in five structures for group A, B1 and B2 images were no significant difference (all p > 0.05), however, the number of temporal bone lesions which involved in mastoid for group B3 images were significantly more than group A (p < 0.05). The radiation dose of high resolution CT protocol and low-dose protocol were 0.55 mSv and 0.11 mSv, respectively. Conclusion: Compared with high resolution CT protocol, in the low-dose protocol of temporal bone CT, DLR mild and standard could improve the objective image quality, maintain good subjective image quality and satisfy clinical diagnosis of otitis media and mastoiditis patients.

Autoimmune Pancreatitis Surveillance: A Simplified MRI Protocol Versus a Comprehensive Pancreatic MRI Protocol.

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) has good diagnostic performance and causes no radiation damage, making it an ideal tool for the autoimmune pancreatitis (AIP) surveillance. However, its time cost is high. This study aimed to evaluate (1) whether a simplified protocol (SP) of MRI for AIP surveillance provides information equivalent to the comprehensive protocol (CP) and (2) the time cost reductions associated with using an SP. MATERIALS AND METHODS: This retrospective single-institutional study included 40 patients with AIP with at least two contrast-enhanced MRI/magnetic resonance cholangiopancreatography studies. Two radiologists evaluated two imaging sets (CP/SP) per patient, independently. Intra- and inter-observer agreement in the evaluation of the pancreas and extrapancreatic organs involvement using the SP/CP in addition to the time cost differences between the SP and CP were assessed. Intra- and inter-rater reliability were assessed using Cohen's kappa test, intraclass correlations, or the weighted kappa test. The differences in time costs between the CP and SP were compared using the Mann-Whitney U test or Wilcoxon signed-rank test. RESULTS: The SP had strong intra- and inter-observer agreement with the CP in evaluating MRI parameters (κ ï¼ž 0.60, moderate to excellent) and disease activity status (κ ï¼ž 0.80, all excellent). The overall image acquisition time cost for the SP was 49.2% of the CP. For the two radiologists, the image interpretation time cost of the SP was reduced by approximately 35% and 27% compared to the CP. CONCLUSION: For AIP surveillance, SP MRI provides information consistent with the CP and is less time-consuming.