Integrating serum pharmacochemistry, network pharmacology and untargeted metabolomics strategies to reveal the material basis and mechanism of action of Feining keli in the treatment of chronic bronchitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Feining keli (FNKL) is herbal preparation mainly made from Senecio cannabifolius Less., In recent years, more and more studies have found that FNKL has excellent therapeutic effects on chronic bronchitis (CB). Nevertheless, its pharmacodynamic material basis and mechanism of action are still unknown. AIM OF THE STUDY: This study aimed to explore the pharmacodynamic material basis and mechanism of action of FNKL in treating CB. MATERIALS AND METHODS: The CB rat model was induced using nasal drops of lipopolysaccharide (LPS) in combination with smoking. Various assessments including behavioral and body mass examination, lung index measurement, enzyme linked immunosorbent assay (ELISA), as well as histological analyses using hematoxylin and eosin (H&E) and Masson staining were conducted to validate the reliability of the CB model. The serum components of FNKL in CB rats were identified using ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). Network pharmacology was used to predict the network of action of the active ingredients in FNKL based on these serum components. Signaling pathways were enriched and analyzed, and molecular docking was conducted for key targets. Molecular dynamics simulations were performed using GROMACS software. The mechanism was confirmed through a series of experiments including Western blot (WB), immunofluorescence (IF), and reverse transcription (RT)-PCR. Additionally, untargeted metabolomics was employed to identify biomarkers and relevant metabolic pathways associated with the treatment of CB with FNKL. RESULTS: In CB rats, FNKL improved body mass, lung index, and pathological damage of lung tissues. It also decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), malonaldehyde (MDA) levels, and percentage of lung collagen fiber area. Furthermore, FNKL increased IL-10 and superoxide dismutase (SOD) levels, which helped alleviate bronchial inflammation in the lungs. A total of 70 FNKL chemical components were identified in CB rat serum. Through network pharmacology analysis, 5 targets, such as PI3K, AKT, NF-κB, HIF-1α, and MYD88, were identified as key targets of FNKL in the treatment of CB. Additionally, the key signaling pathways identified were PI3K/AKT pathway、NF-κB/MyD88 pathway、HIF-1α pathway. WB, IF, and RT-PCR experiments were conducted to confirm the findings. Molecular docking studies demonstrated successful docking of 16 potential active components with 5 key targets. Additionally, molecular dynamics simulations indicated the stability of quercetin-3-galactoside and HIF-1α. Metabolomics analysis revealed that FNKL primarily regulated pathways related to alpha-linolenic acid metabolism, primary bile acid biosynthesis, bile secretion, arachidonic acid metabolism, neuroactive ligand-receptor interaction, and folate biosynthesis. Furthermore, the expression levels of traumatic acid, traumatin, alpha linolenic acid, cholic acid, 2-arachidonoylglycerol, deoxycholic acid, 7,8-dihydroneopterin, and other metabolites were found to be regulated. CONCLUSION: FNKL exhibits positive therapeutic effects on CB, with quercetin-3-galactoside identified as a key active component. The mechanism of FNKL's therapeutic action on CB involves reducing inflammatory response, oxidative stress, and regulating metabolism, and its molecular mechanism was better elucidated in a holistic manner. This study serves as a reference for understanding the pharmacodynamic material basis and mechanism of action of FNKL in treating CB, and provides avenues for exploring the effects of compounded herbal medicines on CB.

Detection and simultaneous imaging of acrylamide, miR-21 and miR-221 based on multicolor aggregation-induced emission nanoparticles and DNAzyme walker.

Acrylamide (AA) in heat-processed foods has emerged as a global health problem, mainly carcinogenic, neurotoxic, and reproductive toxicity, and an increasing number of researchers have delved into elucidating its toxicological mechanisms. Studies have demonstrated that exposure of HepG2 by AA in a range of concentrations can induce the upregulation of miR-21 and miR-221. Monitoring the response of intracellular miRNAs can play an important role in unraveling the mechanisms of AA toxicity. Here, multicolor aggregation induced emission nano particle (AIENP) probes were constructed from three AIE dyes for simultaneous imaging of intracellular AA and AA-induced miR-21/miR-221 by combining the recognition function of AA aptamers and the signal amplification of a DNAzyme walker. The surface of these nanoparticles contains carboxyl groups, facilitating their linkage to a substrate chain modified with a fluorescent quencher group via an amide reaction. Optimization experiments were conducted to determine the optimal substrate-to-DNAzyme ratio, confirming its efficacy as a walker for signal amplification. Sensitive detection of AA, miR-21 and miR-221 was achieved in extracellular medium, with detection limits of 0.112 nM for AA, 0.007 pM and 0.003 pM for miR-21 and miR-221, respectively, demonstrating excellent selectivity. Intracellularly, ZIF-8 structure collapsed, releasing Zn2+, activating DNAzyme cleavage activity, and the fluorescence of multicolor AIENPs within HepG2 cells gradually recovered with increasing stimulation time (0-12 h) and concentrations of AA (0-500 µM). This dynamic response unveiled the relationship between AA exposure and miR-21/miR-221 expression, further validating the carcinogenicity of AA.

Comparison of Mixed Reality-Assisted Spinal Puncture with Landmark-Guided Spinal Puncture by Novice Practitioners: A Pilot Study.

Background: Performing spinal anaesthesia in elderly patients with ligament calcification or hyperostosis is challenging for novice practitioners. This pilot study aimed to compare the effectiveness of mixed reality-assisted spinal puncture (MRasp) with that of landmark-guided spinal puncture (LGsp) by novice practitioners in elderly patients. Methods: In this pilot study, 36 patients (aged ≥65 years) scheduled for elective surgery under spinal anaesthesia by anaesthesiology residents were included. Patients were randomly assigned to the MRasp group (n = 18) or the LGsp group (n = 18). The outcomes included the number of needle insertion attempts, redirection attempts, passes, the rate of successful first-attempt needle insertion, the rate of successful first needle pass, the spinal puncture time, the total procedure time, and the incidence of perioperative complications. Results: The median number of needle insertion attempts was significantly fewer in the MRasp group than in the LGsp group (1.0 vs 2.0, P = 0.023). The proportion of patients with successful first-attempt needle insertion was 72.2% in the MRasp group and 44.4% in the LGsp group (P = 0.176). The incidence of perioperative complications did not significantly differ between the two groups. Conclusion: This pilot study found that novice practitioners made significantly fewer needle insertion attempts in the MRasp group compared to the LGsp group when performing spinal anaesthesia on elderly patients. A future randomized controlled trial (RCT) is warranted to validate its effectiveness. Trial Registration: This trial was registered at https://www.chictr.org.cn/showproj.html?proj=178960 (ChiCTR-IPR-2300068520). Public title: Mixed reality-assisted versus landmark-guided spinal puncture in elderly patients: a randomized controlled pilot study. Principal investigator: Lei Gao. The registration date was February 22, 2023. The date of the first participant enrolment was February 27, 2023.

We developed virtual spine-presenting technology and patented optimal trajectory design technology to assist in spinal puncture and reported that the median number of needle insertion attempts was significantly fewer in the mixed reality-assisted spinal puncture group than in the landmark-guided spinal puncture group.

Cr-Diamond/Cu Composites with High Thermal Conductivity Fabricated by Vacuum Hot Pressing.

Chromium-plated diamond/copper composite materials, with Cr layer thicknesses of 150 nm and 200 nm, were synthesized using a vacuum hot-press sintering process. Comparative analysis revealed that the thermal conductivity of the composite material with a Cr layer thickness of 150 nm increased by 266%, while that with a Cr layer thickness of 200 nm increased by 242%, relative to the diamond/copper composite materials without Cr plating. This indicates that the introduction of the Cr layer significantly enhanced the thermal conductivity of the composite material. The thermal properties of the composite material initially increased and subsequently decreased with rising sintering temperature. At a sintering temperature of 1050 °C and a diamond particle size of 210 µm, the thermal conductivity of the chromium-plated diamond/copper composite material reached a maximum value of 593.67 W∙m-1∙K-1. This high thermal conductivity is attributed to the formation of chromium carbide at the interface. Additionally, the surface of the diamond particles in contact with the carbide layer exhibited a continuous serrated morphology due to the interface reaction. This "pinning effect" at the interface strengthened the bonding between the diamond particles and the copper matrix, thereby enhancing the overall thermal conductivity of the composite material.

New insight into the exotic states strongly coupled with the DD‾∗ from the Tcc.

We have investigated the internal structure of the open- and hidden-charmed (DD∗/D¯D∗) molecules in the unified framework. We first fit the experimental lineshape of the Tcc+ state and extract the DD∗ interaction, from which the Tcc+ is assumed to arise solely. Then we obtain the DD‾∗ interaction by charge conjugation. Our results show that the DD‾∗ interaction is attractive but insufficient to form X(3872) as a bound state. Instead, its formation requires the crucial involvement of the coupled channel effect between the DD¯∗ and cc¯ components, although the cc¯ accounts for approximately 1% only. Besides X(3872), we have obtained a higher-energy state around 3957.9 MeV with a width of 16.7 MeV, which may be a potential candidate for the X(3940). In JPC=1+- sector, we have found two states related to the iso-scalar X̃(3872) and hc(2P), respectively. Our combined study provides valuable insights into the nature of these DD∗/DD¯∗ exotic states.

Cervical facet joint degeneration, facet joint angle and paraspinal muscle degeneration are correlated with degenerative cervical spondylolisthesis at C4/5: a propensity score-matched study.

BACKGROUND CONTEXT: Prior studies have hypothesized that degenerative cervical spondylolisthesis (DCS) may be influenced by loss of stability due to disc, facet joint or cervical alignment. Meanwhile, it is commonly believed that the facet joints and paraspinal muscles participate in maintaining cervical spine stability. However, the impact of paraspinal muscle morphology and detailed facet joint features on DCS requires further investigation. PURPOSE: To compare facet joint characteristics, disc degeneration and muscle morphology between patients with DCS and those without DCS. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Consecutive surgical patients with degenerative cervical spondylosis from June 2016 to August 2023 were recruited. OUTCOME MEASURES: DCS was assessed on X-ray based on the translation distance. Cervical facet joint degeneration (CFD), the facet joint angle on the axial plane (FA-A) and the facet joint angle on the sagittal plane (FA-S), and facet joint tropism (FT) were measured on computerized tomography (CT). Paraspinal muscle degeneration was assessed on magnetic resonance imaging (MRI) including by the adjusted cross-sectional area (aCSA), the functional aCSA, the fat infiltration ratio (FI%). The Pfirrmann grade of the cervical disc was also evaluated. METHODS: Demographic and clinical data were compared in matched and unmatched cohorts. Disc degeneration, muscle degeneration and facet joint characteristics, including FA, FT and CFD, were compared between patients with and without DCS. Furthermore, the degree of CFD was compared with that of adjacent segments in both groups. Additionally, logistic regression was performed to determine independent risk factors for DCS. Finally, the receiver operating characteristic (ROC) curve, area under the curve (AUC) and cutoff value for the risk factors were calculated. RESULTS: A total of 431 surgical patients were propensity score matched for age, sex and BMI, and 146 patients were included in the final analysis, with 73 patients in the DCS group and 73 patients in the non-DCS group. DCS patients exhibited more severe CFD at C4/5 (segment with spondylolisthesis). Additionally, DCS was generally associated with more severe CFD, a more horizontal FA-S, more FT and worse paraspinal muscle health but similar disc degeneration. In addition, anterior spondylolisthesis was related to more severe CFD and decreased functional aCSA of the flexors and extensors. Finally, more severe CFD, a more horizontal FA-S and a higher FI% on deep extensor were revealed to be risk factors for DCS, with cutoff values of 1.5, 44.5̊, and 37.1%, respectively. CONCLUSIONS: This study demonstrated that CFD, the FA and FT and parasipnal muscle degeneration were associated with DCS. And may provide novel insight into the pathogenesis and nature history of DCS and suggest the evolution of degeneration in the cervical spine.

Self-Adhesive, Stretchable, and Thermosensitive Iontronic Hydrogels for Highly Sensitive Neuromorphic Sensing-Synaptic Systems.

Artificial sensory afferent nerves that emulate receptor nanochannel perception and synaptic ionic information processing in chemical environments are highly desirable for bioelectronics. However, challenges persist in achieving life-like nanoscale conformal contact, agile multimodal sensing response, and synaptic feedback with ions. Here, a precisely tuned phase transition poly(N-isopropylacrylamide) (PNIPAM) hydrogel is introduced through the water molecule reservoir strategy. The resulting hydrogel with strongly cross-linked networks exhibits excellent mechanical performance (∼2000% elongation) and robust adhesive strength. Importantly, the hydrogel's enhanced ionic conductance and heterogeneous structure of the temperature-sensitive component enable highly sensitive strain information perception (GFmax = 7.94, response time ∼ 87 ms), temperature information perception (TCRmax = -1.974%/°C, response time ∼ 270 ms), and low energy consumption synaptic plasticity (42.2 fJ/spike). As a demonstration, a neuromorphic sensing-synaptic system is constructed integrating iontronic strain/temperature sensors with fiber synapses for real-time information sensing, discrimination, and feedback. This work holds enormous potential in bioinspired robotics and bioelectronics.

Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

BACKGROUND: Diabetic retinopathy (DR) is the primary cause of visual problems in patients with diabetes. The Heyingwuzi formulation (HYWZF) is effective against DR. AIM: To determine the HYWZF prevention mechanisms, especially those underlying mitophagy. METHODS: Human retinal capillary endothelial cells (HRCECs) were treated with high glucose (hg), HYWZF serum, PX-478, or Mdivi-1 in vitro. Then, cell counting kit-8, transwell, and tube formation assays were used to evaluate HRCEC proliferation, invasion, and tube formation, respectively. Transmission electron microscopy was used to assess mitochondrial morphology, and Western blotting was used to determine the protein levels. Flow cytometry was used to assess cell apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Moreover, C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks. Blood glucose levels and body weight were monitored continuously. Changes in retinal characteristics were evaluated using hematoxylin and eosin, tar violet, and periodic acid-Schiff staining. Protein levels in retinal tissues were determined via Western blotting, immunohistochemistry, and immunostaining. RESULTS: HYWZF inhibited excessive ROS production, apoptosis, tube formation, and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro. It increased the mRNA expression levels of BCL2-interacting protein 3 (BNIP3), FUN14 domain-containing 1, BNIP3-like (BNIP3L, also known as NIX), PARKIN, PTEN-induced kinase 1, and hypoxia-inducible factor (HIF)-1α. Moreover, it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio. However, PX-478 and Mdivi-1 reversed these effects. Additionally, PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy. HYWZF intervention improved the symptoms of diabetes, tissue damage, number of acellular capillaries, and oxidative stress in vivo. Furthermore, in vivo experiments confirmed the results of in vitro experiments. CONCLUSION: HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

Stretchable and Self-Powered Mechanoluminescent Triboelectric Nanogenerator Fibers toward Wearable Amphibious Electro-Optical Sensor Textiles.

Flexible electro-optical dual-mode sensor fibers with capability of the perceiving and converting mechanical stimuli into digital-visual signals show good prospects in smart human-machine interaction interfaces. However, heavy mass, low stretchability, and lack of non-contact sensing function seriously impede their practical application in wearable electronics. To address these challenges, a stretchable and self-powered mechanoluminescent triboelectric nanogenerator fiber (MLTENGF) based on lightweight carbon nanotube fiber is successfully constructed. Taking advantage of their mechanoluminescent-triboelectric synergistic effect, the well-designed MLTENGF delivers an excellent enhancement electrical signal of 200% and an evident optical signal whether on land or underwater. More encouragingly, the MLTENGF device possesses outstanding stability with almost unchanged sensitivity after stretching for 200%. Furthermore, an extraordinary non-contact sensing capability with a detection distance of up to 35 cm is achieved for the MLTENGF. As application demonstrations, MLTENGFs can be used for home security monitoring, intelligent zither, traffic vehicle collision avoidance, and underwater communication. Thus, this work accelerates the development of wearable electro-optical textile electronics for smart human-machine interaction interfaces.

Immunotherapy, prognostic, and tumor biomarker based on pancancer analysis, SMARCD3.

BACKGROUND: SMARCD3 has recently been shown to be an important gene affecting cancer, playing an important role in medulloblastoma and pancreatic ductal adenocarcinoma. Therefore, we conducted this research to investigate the potential involvement of SMARCD3 across cancers and to offer recommendations for future studies. METHODS: Utilizing information on 33 malignancies in the UCSC Xena database, SMARCD3 expression and its prognostic value were assessed. The tumor microenvironment was evaluated with the "CIBERSORT" and "ESTIMATE" algorithms. SMARCD3 and immune-related genes were analyzed using the TISIDB website. The pathways related to the target genes were examined using GSEA. MSI (microsatellite instability), TMB (tumor mutational burden), and immunotherapy analysis were used to evaluate the impact of target genes on the response to immunotherapy. RESULTS: There is heterogeneity in terms of the expression and prognostic value of SMARCD3 among various cancers, but it is a risk factor for many cancers including uterine corpus endometrial cancer (UCEC), renal clear cell carcinoma (KIRC), and gastric adenocarcinoma (STAD). GSEA revealed that SMARCD3 is related to chromatin remodeling and transcriptional activation, lipid metabolism, and the activities of various immune cells. The TMB and MSI analyses suggested that SMARCD3 affects the immune response efficiency of KIRC, LUAD and STAD. Immunotherapy analysis suggested that SMARCD3 may be a potential immunotherapy target. RT-qPCR demonstrated the variation in SMARCD3 expression in KIRC, LUAD, and STAD. CONCLUSION: Our study revealed that SMARCD3 affects the prognosis and immunotherapy response of some tumors, providing a direction for further research on this gene.

Identification Of Endothelial Cell Immune-related Gene Signature for Lung Adenocarcinoma by Integrated Analysis of Single-cell and Bulk RNA Sequencing Data.

Background: The role of endothelial cells in tumor progression is considerable, yet the effect of endothelial cell immune-related genes (EIRGs) is still unclear. This research aimed to scrutinize the prognostic value of EIRGs in lung adenocarcinoma (LUAD) and provide further insights into the abovementioned uncertainties. Methods: After single-cell RNA sequencing (scRNA-seq) samples were obtained from the Gene Expression Omnibus (GEO) database, they were integrated with bulk RNA sequencing data from The Cancer Genome Atlas (TCGA). Prognostic markers were determined and a prognostic model was developed. From this model, a nomogram was constructed. We analyzed the biological mechanism of the EIRGs in LUAD, including functional enrichment, tumor mutational burden (TMB), tumor microenvironment (TME) analyses and drug sensitivity. We validated the signature by validating the external cohort GSE31210 and RT-qPCR. Results: After analyzing the model constructed from eight EIRGs, we observed that high-risk group (HG) LUAD patients (a risk score exceeding 4.65) exhibited unfavorable outcomes according to Kaplan‒Meier survival curves. This outcome was confirmed by GSE31210. The nomogram based on the model demonstrated significant predictive value. HG was influenced primarily by steroid hormone biosynthesis and ECM receptor interactions. The TMB in HGs was greater than that in the LG. Analysis of drug sensitivity revealed the direction for individualized treatment for both risk cohorts. Variations in the expression of EIRGs have been confirmed via RT-qPCR in several LUAD cell lines. Conclusions: The prognostic model and nomogram above are valuable for determining the survival rate and treatment options for LUAD patients.

Dynamic patterns of carbohydrate metabolism genes in bacterioplankton during marine algal blooms.

Carbohydrates play a pivotal role in nutrient recycling and regulation of algal-bacterial interactions. Despite their ecological significance, the intricate molecular mechanisms governing regulation of phycosphere carbohydrates by bacterial taxa linked with natural algal bloom have yet to be fully elucidated. Here, a comprehensive temporal metagenomic analysis was conducted to explore the carbohydrate-active enzyme (CAZyme) genes in two discrete algal bloom microorganisms (Gymnodinium catenatum and Phaeocystis globosa) across three distinct bloom stages: pre-bloom, peak bloom, and post-bloom. Elevated levels of extracellular carbohydrates, primarily rhamnose, galactose, glucose, and arabinose, were observed during the initial and post-peak stages. The prominent CAZyme families identified-glycoside hydrolases (GH) and carbohydrate-binding modules (CBMs)-were present in both algal bloom occurrences. In the G. catenatum bloom, GH23/24 and CBM13/14 were prevalent during the pre-bloom and peak bloom stages, whereas GH2/3/30 and CBM12/24 exhibited increased prevalence during the post-bloom phase. In contrast, the P. globosa bloom had a dominance of GH13/23 and CBM19 in the initial phase, and this was succeeded by GH3/19/24/30 and CBM54 in the later stages. This gene pool variation-observed distinctly in specific genera-highlighted the dynamic structural shifts in functional resources driven by temporal alterations in available substrates. Additionally, ecological linkage analysis underscored a correlation between carbohydrates (or their related genes) and phycospheric bacteria, hinting at a pattern of bottom-up control. These findings contribute to understanding of the dynamic nature of CAZymes, emphasizing the substantial influence of substrate availability on the metabolic capabilities of algal symbiotic bacteria, especially in terms of carbohydrates.

Gefitinib metabolism-related lncRNAs for the prediction of prognosis, tumor microenvironment and drug sensitivity in lung adenocarcinoma.

The complete compound of gefitinib is effective in the treatment of lung adenocarcinoma. However, the effect on lung adenocarcinoma (LUAD) during its catabolism has not yet been elucidated. We carried out this study to examine the predictive value of gefitinib metabolism-related long noncoding RNAs (GMLncs) in LUAD patients. To filter GMLncs and create a prognostic model, we employed Pearson correlation, Lasso, univariate Cox, and multivariate Cox analysis. We combined risk scores and clinical features to create nomograms for better application in clinical settings. According to the constructed prognostic model, we performed GO/KEGG and GSEA enrichment analysis, tumor immune microenvironment analysis, immune evasion and immunotherapy analysis, somatic cell mutation analysis, drug sensitivity analysis, IMvigor210 immunotherapy validation, stem cell index analysis and real-time quantitative PCR (RT-qPCR) analysis. We built a predictive model with 9 GMLncs, which showed good predictive performance in validation and training sets. The calibration curve demonstrated excellent agreement between the expected and observed survival rates, for which the predictive performance was better than that of the nomogram without a risk score. The metabolism of gefitinib is related to the cytochrome P450 pathway and lipid metabolism pathway, and may be one of the causes of gefitinib resistance, according to analyses from the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Immunological evasion and immunotherapy analysis revealed that the likelihood of immune evasion increased with risk score. Tumor microenvironment analysis found most immune cells at higher concentrations in the low-risk group. Drug sensitivity analysis found 23 sensitive drugs. Twenty-one of these drugs exhibited heightened sensitivity in the high-risk group. RT-qPCR analysis validated the characteristics of 9 GMlncs. The predictive model and nomogram that we constructed have good application value in evaluating the prognosis of patients and guiding clinical treatment.

Human Umbilical Cord Mesenchymal Stem Cell-derived Exosome Regulates Intestinal Type 2 Immunity.

AIMS: The aim of this study was to investigate the role of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in regulating the intestinal type 2 immune response for either protection or therapy. BACKGROUND: hUCMSC-Exo was considered a novel cell-free therapeutic product that shows promise in the treatment of various diseases. Type 2 immunity is a protective immune response classified as T-helper type 2 (Th2) cells and is associated with helminthic infections and allergic diseases. The effect of hUCMSC-Exo on intestinal type 2 immune response is not clear. METHOD: C57BL/6 mice were used to establish intestinal type 2 immune response by administering of H.poly and treated with hUCMSC-Exo before or after H.poly infection. Intestinal organoids were isolated and co-cultured with IL-4 and hUCMSC-Exo. Then, we monitored the influence of hUCMSC-Exo on type 2 immune response by checking adult worms, the hyperplasia of tuft and goblet cells. RESULT: hUCMSC-Exo significantly delays the colonization of H.poly in subserosal layer of duodenum on day 7 post-infection and promotes the hyperplasia of tuft cells and goblet cells on day 14 post-infection. HUCMSC-Exo enhances the expansion of tuft cells in IL-4 treated intestinal organoids, and promotes lytic cell death. CONCLUSION: Our study demonstrates hUCMSC-Exo may benefit the host by increasing the tolerance at an early infection stage and then enhancing the intestinal type 2 immune response to impede the helminth during Th2 priming. Our results show hUCMSC-Exo may be a positive regulator of type 2 immune response, suggesting hUCMSC-Exo has a potential therapeutic effect on allergic diseases.

Development of an 18F-labeled azobenzothiazole tracer for α-synuclein aggregates in the brain.

Nuclear imaging of aggregated α-synuclein pathology is an urgent clinical need for Parkinson's disease, yet promising tracers for brain α-synuclein aggregates are still rare. In this work, a class of compact benzothiazole derivatives was synthesized and evaluated for α-synuclein aggregates. Among them, azobenzothiazoles exhibited specific and selective detection of α-synuclein aggregates under physiological conditions. Fluoro-pegylated azobenzothiazole NN-F further demonstrated high-affinity binding to α-synuclein aggregates and efficient 18F-radiolabeling via nucleophilic displacement of a tosyl precursor. [18F]NN-F was stable in plasma in vitro and showed efficient brain uptake with little defluorination in vivo.

The Prevalence of Marine Lipophilic Phycotoxins Causes Potential Risks in a Tropical Small Island Developing State.

Tropical small island developing states (SIDS), with their geographical isolation and limited resources, heavily rely on the fisheries industry for food and revenue. The presence of marine lipophilic phycotoxins (MLPs) poses risks to their economy and human health. To understand the contamination status and potential risks, the Republic of Kiribati was selected as the representative tropical SIDS and 55 species of 256 coral reef fish encompassing multiple trophic levels and feeding strategies were collected to analyze 17 typical MLPs. Our results showed that the potential risks of ciguatoxins were the highest and approximately 62% of fish species may pose risks for consumers. Biomagnification of ciguatoxins was observed in the food web with a trophic magnification factor of 2.90. Brevetoxin-3, okadaic acid, and dinophysistoxin-1 and -2 were first reported, but the risks posed by okadaic acid and dinophysistoxins were found to be negligible. The correlation analysis revealed that fish body size and trophic position are unreliable metrics to indicate the associated risks and prevent the consumption of contaminated fish. The potential risks of MLPs in Kiribati are of concern, and our findings can serve as valuable inputs for developing food safety policies and fisheries management strategies specific to tropical SIDS contexts.

Treatment strategies for stage IA non-small cell lung cancer: A SEER-based population study.

BACKGROUND: There are various therapeutic methods for treating stage IA (T1N0M0) non-small cell lung cancer (NSCLC), but no studies have systematically assessed multiple treatments to determine the most effective therapy. METHODS: Stage IA NSCLC patient data collected between 2004 and 2018 were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. Treatment modalities included observation, chemotherapy alone (CA), radiation alone (RA), radiation+chemotherapy (RC), surgery alone (SA), surgery+chemotherapy (SC), surgery+radiation (SR) and surgery+radiation+chemotherapy (SRC). Comparisons were made of overall survival (OS) and lung cancer-specific survival (LCSS) among patients based on different therapeutic methods by survival analysis. RESULTS: Ultimately, 89147 patients with stage IA NSCLC between 2004 and 2018 were enrolled in this study. The order of multiple treatment modalities based on the hazard ratio (HR) for OS for the entire cohort revealed the following results: SA (HR: 0.20), SC (HR: 0.25), SR (HR: 0.42), SRC (HR: 0.46), RA (HR: 0.56), RC (HR: 0.72), CA (HR: 0.91) (P<0.001), and observation (HR: Ref). The SA group had the best OS and LCSS, and similar results were found in most subgroup analyses (all P<0.001). The order of surgical modalities based on the HR for OS for the entire cohort revealed the following results: lobectomy (HR: 0.32), segmentectomy (HR: 0.41), wedge resection (HR: 0.52) and local tumor destruction (HR: Ref). Lobectomy had the best effects on OS and LCSS, and similar results were found in all subgroup analyses (all P<0.001). CONCLUSION: SA appeared to be the optimal treatment modality for patients with stage IA NSCLC, and lobectomy was associated with the best prognosis. There may be some indication and selection bias in our study, and the results of this study should be confirmed in a prospective study.