Modified Zhenwu Decoction suppresses chronic colitis via targeting macrophage CCR2/Fyn/p38 MAPK signaling axis.

BACKGROUND: Ulcerative colitis (UC) is associated with intestinal macrophage infiltration due to disruption of the mucosal barrier and bacterial invasion. Therefore, it is crucial to identify therapeutic agents capable of attenuating the macrophage-induced inflammatory response to preserve mucosal homeostasis and immune tolerance. The modified Zhenwu decoction (CDD-2103) is a novel herbal formulation developed based on the principles of Traditional Chinese medicine. To date, there are no clinically approved herbal formulations for UC with a well-known mechanism of action on macrophages. PURPOSE: The objective of this study was to systematically investigate the inhibitory effect of the active fraction of CDD-2103 in a mouse model of chronic colitis and delineate the mechanisms underlying its inhibitory action. METHODS: CDD-2103 was extracted into four fractions using organic solvents with increasing polarity. A chronic 49-day dextran sulfate sodium (DSS)-induced colitis mice model, closely resembling human clinical conditions, was used to examine the effect of CDD-2103 on chronic colitis. To confirm the effect of CDD-2103 on macrophages in this chronic colitis model, adoptive macrophage transfer and CCL2 supplementation were conducted. The mechanisms of action of CDD-2103 were further elucidated utilizing bone marrow-derived macrophages (BMDMs). Transcriptome analysis was conducted to gain insights into the underlying mechanism of action of CDD-2103 in BMDMs. RESULTS: Our in vitro and in vivo findings demonstrated that the ethanol-enriched fraction of CDD-2103 exhibited significant anti-inflammatory effects, leading to the suppression of colitis severity. This effect was associated with diminished accumulation of colonic macrophages in the lamina propria of CDD-2103-intervened colitis mice. Specifically, CDD-2103 inhibited CCR2/L2-mediated proinflammatory macrophage infiltration into the colon without affecting macrophage proliferation. Mechanistically, CDD-2103 inhibited Fyn expression-mediated p38 MAPK activation and subsequently suppressed CCR2 expression in BMDMs. CONCLUSIONS: Collectively, our study supports the potential use of CDD-2103 to limit macrophage infiltration, thereby reducing inflammation during UC treatment. CDD-2103 and the components in the ethanolic fraction are promising candidates for the development of novel drugs for UC management. Additionally, our study underscores Fyn-mediated CCR2 expression as a potential therapeutic target for the management of UC.

The biological response of pH-switch-based gold nanoparticle-composite polyamino acid embolic material.

With continuous advances in medical technology, non-invasive embolization has emerged as a minimally invasive treatment, offering new possibilities in cancer therapy. Fluorescent labeling can achieve visualization of therapeutic agents in vivo, providing technical support for precise treatment. This paper introduces a novel in situ non-invasive embolization composite material, Au NPs@(mPEG-PLGTs), created through the electrostatic combination of L-cysteine-modified gold nanoparticles (Au NPs) and methoxy polyethylene glycol amine-poly[(L-glutamic acid)-(L-tyrosine)] (mPEG-PLGTs). Experiments were undertaken to confirm the biocompatibility, degradability, stability and performance of this tumor therapy. The research results demonstrated a reduction in tumor size as early as the fifth day after the initial injection, with a significant 90% shrinkage in tumor volume observed after a 20-day treatment cycle, successfully inhibiting tumor growth and exhibiting excellent anti-tumor effects. Utilizing near-infrared in vivo imaging, Au NPs@(mPEG-PLGTs) displayed effective fluorescence tracking within the bodies of nude BALB-c mice. This study provides a novel direction for the further development and innovation of in situ non-invasive embolization in the field, highlighting its potential for rapid, significant therapeutic effects with minimal invasiveness and enhanced safety.

Tumor-derived extracellular vesicles regulate macrophage polarization: role and therapeutic perspectives.

Extracellular vesicles (EVs) are important cell-to-cell communication mediators. This paper focuses on the regulatory role of tumor-derived EVs on macrophages. It aims to investigate the causes of tumor progression and therapeutic directions. Tumor-derived EVs can cause macrophages to shift to M1 or M2 phenotypes. This indicates they can alter the M1/M2 cell ratio and have pro-tumor and anti-inflammatory effects. This paper discusses several key points: first, the factors that stimulate macrophage polarization and the cytokines released as a result; second, an overview of EVs and the methods used to isolate them; third, how EVs from various cancer cell sources, such as hepatocellular carcinoma, colorectal carcinoma, lung carcinoma, breast carcinoma, and glioblastoma cell sources carcinoma, promote tumor development by inducing M2 polarization in macrophages; and fourth, how EVs from breast carcinoma, pancreatic carcinoma, lungs carcinoma, and glioblastoma cell sources carcinoma also contribute to tumor development by promoting M2 polarization in macrophages. Modified or sourced EVs from breast, pancreatic, and colorectal cancer can repolarize M2 to M1 macrophages. This exhibits anti-tumor activities and offers novel approaches for tumor treatment. Therefore, we discovered that macrophage polarization to either M1 or M2 phenotypes can regulate tumor development. This is based on the description of altering macrophage phenotypes by vesicle contents.

A blood-brain barrier- and blood-brain tumor barrier-penetrating siRNA delivery system targeting gliomas for brain tumor immunotherapy.

Glioma is recognized as the most infiltrative and lethal form of central nervous system tumors and is known for its limited response to standard therapeutic interventions, high recurrence rate, and unfavorable prognosis. Recent progress in gene and immunotherapy presents a renewed sense of optimism in the treatment of glioblastoma. However, the barriers to overcome include the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), as well as the suppressive immune microenvironment. Overcoming these barriers remains a significant challenge. Here, we developed a lipid nanoparticle platform incorporating a dual-functional peptide (cholesterol-DP7-ACP-T7-modified DOTAP or DAT-LNP) capable of targeting glioma across the BBB and BBTB for brain tumor immunotherapy. This system was designed to achieve two key functions. First, the system could effectively penetrate the BBB during accumulation within brain tissue following intravenous administration. Second, this system enhances the maturation of dendritic cells, the polarization of M1 macrophages, and the activation of cytotoxic CD8+ T cells. This multifaceted approach effectively mitigates the immunosuppressive tumor microenvironment of glioma and promotes robust antitumor immune responses. Overall, the intravenous administration of the delivery system designed in this study demonstrates significant therapeutic potential for glioma and holds promising applications in the field of cancer immunotherapy.

Cotransport of aged biochar colloids and thallium(I) in water-saturated porous media: Impact of the ionic strength, pH and aging degree.

Biochar colloids entering the soil undergo aging over time and exhibit strong capabilities in adsorbing and transporting pollutants. Therefore, investigating the cotransport of aged biochar colloids and thallium (Tl(I)) in quartz sand media is crucial for understanding Tl(I) migration in underground environments. This study investigated the migration of biochar colloids with two different aging degrees and Tl(I) in quartz sand media at various pH and ionic strengths (ISs). The results revealed that under all ISs and pH, 30%AWB (biochar aged with 30 % (w/w) HNO3) inhibited Tl(I) migration in media. This inhibition primarily arose from the introduction of hydroxyl and carboxyl groups during aging, which significantly enhanced colloid adsorption onto Tl(I). At lower ISs, 30%AWB colloids exhibited greater inhibition of Tl(I) migration due to their increased adsorption capacity. Additionally, aging promoted the migration of biochar colloids in the media. Greater biochar aging notably enhanced this promotion, potentially owing to reduced colloidal particle size and the formation of biochar derivatives. Moreover, 50%AWB (biochar aged with 50 % (w/w) HNO3) inhibited Tl(I) migration under low ISs but had almost no impact under high ISs. Nonetheless, at high pH, 50%AWB colloids facilitated Tl(I) migration. This phenomenon might be attributed to the inhibitory effect of aged biochar colloids on Tl(I) adsorption onto media at a high pH, as well as the stable binding between Tl(I) and aged biochar colloids. This study discusses the cotransport of biochar with various degrees of aging and Tl(I) in media, providing insights into remediating soils contaminated with Tl.

A New Bacillus velezensis Strain CML532 Improves Chicken Growth Performance and Reduces Intestinal Clostridium perfringens Colonization.

Bacillus velezensis has gained increasing recognition as a probiotic for improving animal growth performance and gut health. We identified six B. velezensis strains from sixty Bacillus isolates that were isolated from the cecal samples of fifteen different chicken breeds. We characterized the probiotic properties of these six B. velezensis strains. The effect of a selected strain (B. velezensis CML532) on chicken growth performance under normal feeding and Clostridium perfringens challenge conditions was also evaluated. The results revealed that the six B. velezensis strains differed in their probiotic properties, with strain CML532 exhibiting the highest bile salt and acid tolerance and high-yield enzyme and antibacterial activities. Genomic analyses showed that genes related to amino acid and carbohydrate metabolism, as well as genes related to starch and cellulose hydrolysis, were abundant in strain CML532. Dietary supplementation with strain CML532 promoted chicken growth, improved the gut barrier and absorption function, and modulated the gut microbiota. Under the C. perfringens challenge condition, strain CML532 alleviated intestinal damage, reduced ileal colonization of C. perfringens, and also improved chicken growth performance. Collectively, this study demonstrated that the newly isolated B. velezensis strain is a promising probiotic with beneficial effects on chicken growth performance and gut health.

Chemoenzymatic Asymmetric Synthesis of Chiral Triazole Fungicide (R)-Tebuconazole in High Optical Purity Mediated by an Epoxide Hydrolase from Rhodotorula paludigensis.

Tebuconazole is a chiral triazole fungicide used globally in agriculture as a racemic mixture, but its enantiomers exhibit significant enantioselective dissimilarities in bioactivity and environmental behaviors. The steric hindrance caused by the tert-butyl group makes it a great challenge to synthesize tebuconazole enantiomers. Here, we designed a simple chemoenzymatic approach for the asymmetric synthesis of (R)-tebuconazole, which includes the biocatalytic resolution of racemic epoxy-precursor (2-tert-butyl-2-[2-(4-chlorophenyl)ethyl] oxirane, rac-1a) by Escherichia coli/Rpeh whole cells expressed epoxide hydrolase from Rhodotorula paludigensis (RpEH), followed by a one-step chemocatalytic synthesis of (R)-tebuconazole. It was observed that (S)-1a was preferentially hydrolyzed by E. coli/Rpeh, whereas (R)-1a was retained with a specific activity of 103.8 U/g wet cells and a moderate enantiomeric ratio (E value) of 13.4, which was remarkably improved to 43.8 after optimizing the reaction conditions. Additionally, a gram-scale resolution of 200 mM rac-1a was performed using 150 mg/mL E. coli/Rpeh wet cells, resulting in the retention of (R)-1a in a 97.0% ees, a 42.5% yields, and a 40.5 g/L/d space-time yield. Subsequently, the synthesis of highly optical purity (R)-tebuconazole (>99% ee) was easily achieved through the chemocatalytic ring-opening of the epoxy-precursor (R)-1a with 1,2,4-triazole. To elucidate insight into the enantioselectivity, molecular docking simulations revealed that the unique L-shaped substrate-binding pocket of RpEH plays a crucial role in the enantioselective recognition of bulky 2,2-disubstituted oxirane 1a.

Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. OBJECTIVES: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. METHODS: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1-/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. RESULTS: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1-/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. CONCLUSION: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.

Molecularly imprinted metal-organic frameworks assisted cloth and paper hybrid microfluidic devices for visual detection of gonyautoxin.

Marine algal toxin contamination is a major threat to human health. Thus, it is crucial to develop rapid and on-site techniques for detecting algal toxins. In this work, we developed colorimetric cloth and paper hybrid microfluidic devices (µCPADs) for rapid detection of gonyautoxin (GTX1/4) combined with molecularly imprinted polymers. In addition, the metal-organic frameworks (MOFs) composites were applied for this approach by their unique features. Guanosine serves as a dummy template for surface imprinting and has certain structural advantages in recognizing gonyautoxin. MOF@MIPs composites were able to perform a catalytic color reaction using hydrogen peroxide-tetramethylbenzidine for the detection of GTX1/4. The cloth-based sensing substrates were assembled on origami µPADs to form user-friendly, miniaturized colorimetric µCPADs. Combined with a smartphone, the proposed colorimetric µCPADs successfully achieved a low limit of detection of 0.65 µg/L within the range of 1-200 µg/L for rapid visual detection of GTX1/4. Moreover, the GTX1/4 of real shellfish and seawater samples were satisfactorily detected to indicate the application prospect of the µCPADs. The proposed method shows good potential in the low-cost, stable establishment of assays for the rapid detection of environmental biotoxins.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy for acquired port-wine stain at lower extremity: Two case reports.

Two cases of acquired port-wine stain (APWS) at lower extremity were treated with hematoporphyrin monomethyl ether (HMME) and 532 nm LED green light-mediated photodynamic therapy (HMME-PDT). No serious adverse reactions were observed during or post-treatment period. Five-month follow-up showed significant reduction of red patches after a single HMME-PDT treatment in both cases.

Endoscopic resection vs. endoscopic resection plus chemoradiation for T1 stage colorectal cancer: a real-world retrospective cohort study.

Background: Early-stage colorectal cancer (CRC) patients treated with either endoscopic resection (ER) alone or combined ER with chemoradiotherapy (CRT) have unknown survival rates. A national descriptive epidemiological study was conducted to compare the long-term survival of patients with T1 stage CRC with or without the two different treatment options. Methods: Our study identified the records of patients with T1-stage CRC between 2010 and 2018 by searching the Surveillance, Epidemiology, and End Results (SEER) database. Long-term survival was compared using Kaplan-Meier methods and Cox proportional hazard models based on patient demographic and cancer parameters. Results: After propensity score matching (PSM), 825 T1-stage CRC patients were finally enrolled in this study, with 718 patients treated with ER and 107 patients treated with ER + CRT. The overall survival (OS) and cancer specific survival (CSS) rates were similar between the two treatment options (OS: P=0.47; CSS: P=0.28). According to subgroup analysis, older patients and patients with rectal tumor locations exhibited significantly higher OS and CSS rates in the ER + CRT group than in the ER group (OS: P<0.0001; CSS: P<0.0001). Conclusions: The findings from the SEER database showed that OS and CSS rates were similar between the ER and ER + CRT treated groups. Older patients and patients with rectal cancer benefited the most from ER + CRT treatment.

Serum fetuin-a and risk of thoracic aortic aneurysms: a two-sample mendelian randomization study.

Background: Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal. Methods: A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis. Results: Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, P = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (ß = -0.086, standard error (SE) 0.036, P = 0.017). Conclusions: Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.

Identification of Potent siRNA Delivery Peptides Using Computer Modeling.

Peptides with suitable aggregation behavior and electrical properties are potential siRNA delivery vectors. However, identifying suitable peptides with ideal delivery and safety features is difficult owing to the variations in amino acid sequences. Here, a holistic program based on computer modeling and single-cell RNA sequencing (scRNA-seq) is used to identify ideal siRNA delivery peptides. Stage one of this program consists of a sequential screening process for candidates with ideal assembly and delivery ability; stage two is a cell subtype-level analysis program that screens for high in vivo tissue safety. The leading candidate peptide selected from a library containing 12 amino acids showed strong lung-targeted siRNA delivery capacity after hydrophobic modification. Systemic administration of these compounds caused the least damage to liver and lung tissues and has little impact on macrophage and neutrophil numbers. By loading STAT3 siRNA, strong anticancer effects are achieved in multiple models, including patient-derived xenografts (PDX). This screening procedure may facilitate the development of peptide-based RNA interference (RNAi) therapeutics.

Dynamic changes of endothelial and stromal cilia are required for the maintenance of corneal homeostasis.

Primary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α-smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.

Small extracellular vesicles promote the formation of the pre-metastatic niche through multiple mechanisms in colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent global malignancies, posing significant threats to human life and health due to its high recurrence and metastatic potential. Small extracellular vesicles (sEVs) released by CRC play a pivotal role in the formation of the pre-metastatic niche (PMN) through various mechanisms, preparing the groundwork for accelerated metastatic invasion. This review systematically describes how sEVs promote CRC metastasis by upregulating inflammatory factors, promoting immunosuppression, enhancing angiogenesis and vascular permeability, promoting lymphangiogenesis and lymphatic network remodeling, determining organophilicity, promoting stromal cell activation and remodeling and inducing the epithelial-to-mesenchymal transition (EMT). Furthermore, we explore potential mechanisms by which sEVs contribute to PMN formation in CRC and propose novel insights for CRC diagnosis, treatment, and prognosis.

M2 Microglia-derived Exosomes Promote Spinal Cord Injury Recovery in Mice by Alleviating A1 Astrocyte Activation.

M2 microglia transplantation has previously demonstrated beneficial effects on spinal cord injury (SCI) by regulating neuroinflammation and enhancing neuronal survival. Exosomes (EXOs), secreted by almost all cell types, embody partial functions and properties of their parent cells. However, the effect of M2 microglia-derived EXOs (M2-EXOs) on SCI recovery and the underlying molecular mechanisms remain unclear. In this study, we isolated M2-EXOs and intravenously introduced them into mice with SCI. Considering the reciprocal communication between microglia and astroglia in both healthy and injured central nervous systems (CNSs), we subsequently focused on the influence of M2-EXOs on astrocyte phenotype regulation. Our findings indicated that M2-EXOs promoted neuron survival and axon preservation, reduced the lesion area, inhibited A1 astrocyte activation, and improved motor function recovery in SCI mice. Moreover, they inhibited the nuclear translocation of p65 and the activation of the NF-κB signalling pathway in A1 astrocytes. Therefore, our research suggests that M2-EXOs mitigate the activation of neurotoxic A1 astrocytes by inhibiting the NF-κB signalling pathway, thereby improving spinal tissue preservation and motor function recovery following SCI. This positions M2-EXOs as a promising therapeutic strategy for SCI.

The effects of psychiatric disorders on the risk of chronic heart failure: a univariable and multivariable Mendelian randomization study.

Background: Substantial evidence suggests an association between psychiatric disorders and chronic heart failure. However, further investigation is needed to confirm the causal relationship between these psychiatric disorders and chronic heart failure. To address this, we evaluated the potential effects of five psychiatric disorders on chronic heart failure using two-sample Mendelian Randomization (MR). Methods: We selected single nucleotide polymorphisms (SNPs) associated with chronic heart failure and five psychiatric disorders (Attention-Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Major Depression, Bipolar Disorder and Schizophrenia (SCZ)). Univariable (UVMR) and multivariable two-sample Mendelian Randomization (MVMR) were employed to assess causality between these conditions. Ever smoked and alcohol consumption were controlled for mediating effects in the multivariable MR. The inverse variance weighting (IVW) and Wald ratio estimator methods served as the primary analytical methods for estimating potential causal effects. MR-Egger and weighted median analyses were also conducted to validate the results. Sensitivity analyses included the funnel plot, leave-one-out, and MR-Egger intercept tests. Additionally, potential mediators were investigated through risk factor analyses. Results: Genetically predicted heart failure was significantly associated with ADHD (odds ratio (OR), 1.12; 95% CI, 1.04-1.20; p = 0.001), ASD (OR, 1.29; 95% CI, 1.07-1.56; p = 0.008), bipolar disorder (OR, 0.89; 95% CI, 0.83-0.96; p = 0.001), major depression (OR, 1.15; 95% CI, 1.03-1.29; p = 0.015), SCZ (OR, 1.04; 95% CI, 1.00-1.07; p = 0.024). Several risk factors for heart failure are implicated in the above cause-and-effect relationship, including ever smoked and alcohol consumption. Conclusion: Our study demonstrated ADHD, ASD, SCZ and major depression may have a causal relationship with an increased risk of heart failure. In contrast, bipolar disorder was associated with a reduced risk of heart failure, which could potentially be mediated by ever smoked and alcohol consumption. Therefore, prevention strategies for heart failure should also incorporate mental health considerations, and vice versa.

Construction of thermally stable Tb3+-activated green-emitting phosphors: dual driving strategy of doping concentration and excitation wavelength.

The realization of thermally stable Tb3+-doped green emission at high temperatures in solid-state lighting is still a crucial challenge. Nevertheless, the study on modulating the thermally stable luminescence at high temperatures is seldom reported. The position of the intervalence charge transfer (IVCT) energy level is used to systematically investigate the thermal quenching performance of Tb3+-activated green-emitting phosphors with varying concentration gradients of Gd1-xTaO4:xTb3+ (x = 0.1%, 0.5%, and 2%) in this study. The IVCT energy levels were determined according to the empirical formula to show a decreasing trend, consistent with the position of the IVCT energy levels measured in the excitation and diffuse reflectance spectra. Moreover, the thermal quenching performance of different wavelength excitation positions (host absorption, 4f-5d of Tb3+, and Tb3+-Ta5+ IVCT band) is quite different. The modulation of thermal quenching performance among distinct phosphors when subjected to host excitation or IVCT excitation can be elucidated through optimal positions within the energy levels associated with IVCT. The diverse concentration gradient samples exhibit varying degrees of thermal quenching performance in the variable-temperature spectra. The fluorescence lifetimes of the samples are generally comparable but slightly lower. The quantum efficiency rapidly improves as the Tb concentration increases. The underlying mechanism governing this phenomenon is elucidated by constructing a model that encapsulates the interplay between the compensating and quenching channels, in addition to the energy conversion of Tb3+ into Gd3+. The abovementioned results indicate that the dual driving scheme of the doping concentration and excitation wavelength is an effective means to regulate the thermal quenching performance of Tb-activated green-emitting tantalate phosphors.

Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children.

BACKGROUND: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited. METHODS: We conducted single-cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. RESULTS: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. CONCLUSION: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.