A lysosomal-targeted and viscosity-ultrasensitive near-infrared fluorescent probe for sensing viscosity in cells and a diabetic mice model.

Diabetes, as a metabolic disorder, has been implicated in organ dysfunction, often correlated with aberrant changes in viscosity. Lysosomal viscosity serves as an indicator of the lysosome's condition and activity, as it always varies synchronously with the change of lysosome's positioning, structure, and internal constituents. Diabetes, a condition within the metabolic disease category, has the potential to disrupt organ function due to irregular changes in viscosity. Therefore, early and precise diagnosis of diabetes is crucial for the prevention and management of diabetic conditions. Understanding the correlation between viscosity variations and lysosomal changes in vivo is vitally important for researching associated diseases. In this study, we developed Lyso-V, a near-infrared (NIR) fluorescent probe targeting lysosomes, with ultrasensitivity to viscosity changes. This probe, designed with a donor-π-bridge-acceptor (D-π-A) structure, exhibits a significant increase in NIR fluorescence intensity (approximately 690 times) when responding to viscosity, due to a twisted intramolecular charge transfer (TICT) mechanism. Furthermore, the probe designed specifically for lysosomes, enables the detection of changes in lysosomal viscosity as well as autophagy processes. Notably, through the application of this probe, we have detected an increased viscosity within the pathological model of the diabetic mouse. Moreover, Lyso-V was employed to measure the viscosity in diabetic mice. Owing to the multifaceted nature of the Lyso-V probe, it is anticipated to act as a practical and potent resource for deepening our understanding of the pathophysiological aspects of diabetes and aiding in its early detection.

Distinct roles of H3K27me3 and H3K36me3 in vernalization response, maintenance, and resetting in winter wheat.

Winter plants rely on vernalization, a crucial process for adapting to cold conditions and ensuring successful reproduction. However, understanding the role of histone modifications in guiding the vernalization process in winter wheat remains limited. In this study, we investigated the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field. Two core histone modifications, H3K27me3 and H3K36me3, exhibited opposite patterns on the key vernalization gene VERNALIZATION1 (VRN1), correlating with its induction during cold exposure. Moreover, the H3K36me3 level remained high at VRN1 after cold exposure, which may maintain its active state. Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM (TaFIE) and SET DOMAIN GROUP 8/EARLY FLOWERING IN SHORT DAYS (TaSDG8/TaEFS), components of the writer complex for H3K27me3 and H3K36me3, respectively, affected flowering time. Intriguingly, VRN1 lost its high expression after the cold exposure memory in the absence of H3K36me3. During embryo development, VRN1 was silenced with the removal of active histone modifications in both winter and spring wheat, with selective restoration of H3K27me3 in winter wheat. The mutant of Tafie-cr-87, a component of H3K27me3 "writer" complex, did not influence the silence of VRN1 during embryo development, but rather attenuated the cold exposure requirement of winter wheat. Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering. This study unveils distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response, maintenance, and resetting in winter wheat.

Effects of Curing Temperature on Expansion of Concrete Due to ASR.

In the laboratory study of alkali-silica reaction (ASR), models attempt to predict the service life of concrete due to ASR by correlating the performance of concrete at high and low temperatures. However, the consequences of elevating temperature are not so encouraging. In this paper, the influence of temperature on the expansion of 2-graded concrete and 3-graded concrete caused by ASR was investigated by curing the concrete under different temperatures ranging from 40 °C to 80 °C. Increased temperature resulted in rapid expansion at the early stages, but the expansion rate of concrete prisms cured at the higher temperatures (70 °C and 80 °C) was slowed down at the later stages, and concrete prisms cured at 50 °C or 60 °C showed the highest expansions during the experimental period. The chemical analysis results of the pore solution expressed from the concrete show that the ASR expansion is significantly influenced by the [OH-]: the decrease in [OH-] leads to the retardation of the ASR expansion. The decrease in [OH-] is attributed to the consumption of OH- ions for the alkali-silica reaction and the decrease in activity of NaOH(aq) influenced by the temperature. For large cross-section specimens, the OH- within the concrete for alkali-silica reactions cannot be effectively compensated by the external alkali solution. In the accelerated test to evaluate ASR for large cross-section specimens, a curing temperature of less than 60 °C is suggested. This study provides critical insights into the temperature dependency of ASR expansion of concrete, offering a curing temperature range for developing predictive models of ASR expansion under varied environmental conditions.

Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection.

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Peiminine ameliorates Crohn's disease-like colitis by enhancing the function of the intestinal epithelial barrier through Nrf2/HO1 signal.

BACKGROUND AND AIMS: Impaired intestinal barrier function is key in maintaining intestinal inflammation in Crohn's disease (CD). However, no targeted treatment in clinical practice has been developed. Peiminine (Pm) strongly protects the epithelial barrier, the purpose of this study is to investigate whether Pm affects CD-like colitis and potential mechanisms for its action. METHODS: Trinitro-benzene-sulfonic acid (TNBS)-induced mice and Il-10-/- mice were used as CD animal models. Colitis symptoms, histological analysis, and intestinal barrier permeability were used to assess the Pm's therapeutic effect on CD-like colitis. The colon organoids were induced by TNF-α to evaluate the direct role of Pm in inhibiting apoptosis of the intestinal epithelial cells. Western blotting and small molecule inhibitors were used to investigate further the potential mechanism of Pm in inhibiting apoptosis of intestinal epithelial cells. RESULTS: Pm treatment reduced body weight loss, disease activity index (DAI) score, and inflammatory score, demonstrating that colonic inflammation in mice were alleviated. Pm decreased the intestinal epithelial apoptosis, improved the intestinal barrier function, and prevented the loss of tight junction proteins (ZO1 and claudin-1) in the colon of CD mice and TNF-α-induced colonic organoids. Pm activated Nrf2/HO1 signaling, which may protect intestinal barrier function. CONCLUSIONS: Pm inhibits intestinal epithelial apoptosis in CD mice by activating Nrf2/HO1 pathway. This partially explains the potential mechanism of Pm in ameliorating intestinal barrier function in mice and provides a new approach to treating CD.

Durability of Prestressed Piles in a Leachate Environment.

Prestressed pipe piles are common concrete components characterized by dense concrete structures and favorable mechanical properties, and thus, extensively used as coastal soft soil foundations. However, their durability in harsh environments has not been fully clarified. In this study, leachate from an actual landfill site was collected from the east coast of China as the corrosive medium, and the corrosion process was accelerated by electrifying prestressed pipe piles. The results demonstrated that the concentration of chloride ions in the concrete of the prestressed pile increased with the increase in corrosion time. Moreover, the experimental corrosion of these prestressed piles in the drying-wetting cycle proved to be the most severe. However, a protective layer of epoxy resin coating can effectively inhibit the diffusion of chloride ions into the interior of the piles. The final theoretical corrosion amounts of the piles were 1.55 kg, 1.20 kg, and 1.64 kg under immersion, epoxy resin protection, and a drying-wetting cycle environment. The application of epoxy resin reduced chloride penetration by 22.6%, and the drying-wetting cycle increased chloride penetration by 5.8%, respectively, with corresponding corrosion potentials following similar patterns. The actual corrosion depth of the welding seam was 3.20 mm, and there was a large corrosion allowance compared with the requirement (6.53 mm) for the ultimate bending moment. In summary, these prestressed piles exhibited good durability in a leachate environment.

Tumor metabolic activity is associated with subcutaneous adipose tissue radiodensity and survival in non-small cell lung cancer.

BACKGROUND: Cachexia-associated body composition alterations and tumor metabolic activity are both associated with survival of cancer patients. Recently, subcutaneous adipose tissue properties have emerged as particularly prognostic body composition features. We hypothesized that tumors with higher metabolic activity instigate cachexia related peripheral metabolic alterations, and investigated whether tumor metabolic activity is associated with body composition and survival in patients with non-small-cell lung cancer (NSCLC), focusing on subcutaneous adipose tissue. METHODS: A retrospective analysis was performed on a cohort of 173 patients with NSCLC. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans obtained before treatment were used to analyze tumor metabolic activity (standardized uptake value (SUV) and SUV normalized by lean body mass (SUL)) as well as body composition variables (subcutaneous and visceral adipose tissue radiodensity (SAT/VAT radiodensity) and area; skeletal muscle radiodensity (SM radiodensity) and area). Subjects were divided into groups with high or low SAT radiodensity based on Youden Index of Receiver Operator Characteristics (ROC). Associations between tumor metabolic activity, body composition variables, and survival were analyzed by Mann-Whitney tests, Cox regression, and Kaplan-Meier analysis. RESULTS: The overall prevalence of high SAT radiodensity was 50.9% (88/173). Patients with high SAT radiodensity had shorter survival compared with patients with low SAT radiodensity (mean: 45.3 vs. 50.5 months, p = 0.026). High SAT radiodensity was independently associated with shorter overall survival (multivariate Cox regression HR = 1.061, 95% CI: 1.022-1.101, p = 0.002). SAT radiodensity also correlated with tumor metabolic activity (SULpeak rs = 0.421, p = 0.029; SUVpeak rs = 0.370, p = 0.048). In contrast, the cross-sectional areas of SM, SAT, and VAT were not associated with tumor metabolic activity or survival. CONCLUSION: Higher SAT radiodensity is associated with higher tumor metabolic activity and shorter survival in patients with NSCLC. This may suggest that tumors with higher metabolic activity induce subcutaneous adipose tissue alterations such as decreased lipid density, increased fibrosis, or browning.

Influence of Different Types of Fillers on the Performance of PMMA-Based Low-Temperature Rapid Repair Mortar.

In order to further optimize the performance of PMMA (Polymethyl Methacrylate) repair mortar. In this paper, fly ash, talcum powder and wollastonite powder are used as fillers to modify the PMMA repair mortar. The effects of these three fillers on the working performance, mechanical performance and durability of PMMA repair mortar were explored. The study shows that the three fillers have good effect on the bond strength of the repair mortar, in which the fly ash has the best effect on the mechanical performance. The mechanical properties of PMMA repair mortar were best when the amount of fly ash was 60 phr (parts per hundred, representing the amount of the material added per hundred parts of PMMA). At this time, the 28 d compressive strength was 71.26 MPa and the 28 d flexural strength was 28.09 MPa, which increased by 13.31% and 15.33%, respectively. Wollastonite powder had the least negative effect on the setting time of the PMMA repair mortar. When the dosage of wollastonite powder was increased to 100 phr, the setting time was only extended from 65 min to 94 min. When the talc dosage was 60 phr, the best improvement in salt freezing resistance was achieved. After 100 cycles of salt freezing, the mass loss rate and strength loss rate decreased to 0.159% and 4.97%, respectively, which were 75.1% and 37.7% higher than that of the control group. The addition of all three fillers reduced the porosity and the proportion of harmful pores in the mortar. This study contributes to a comprehensive understanding how different types of fillers affect PMMA repair mortars, and it also provides theoretical support for the further development of low-temperature rapid repair mortars.

Kinetics of Alkali-Silica Reaction: Application to Sandstone.

Despite extensive research, the relationship between the progression of the alkali-silica reaction (ASR) and the expansion of concrete due to ASR, particularly for the heterogeneous aggregate with slow reactivity, is not thoroughly understood. In this paper, the dissolution kinetics of reactive silica present in sandstone when exposed to NaOH solutions, alongside the expansion characteristics of rock prisms under ASR conditions, were studied. The experimental results indicate that ASR behaves as a first-order reaction, accompanied by an exponential decrease in the concentration of OH- over time, and the dissolution rate of silica is predominantly governed by diffusion dynamics. Notably, increasing the temperature accelerates ASR, which augments the expansive pressure in a confined and limited space, leading to more significant aggregate expansion. Conversely, higher temperatures also result in a diminished retention of ASR gels within the aggregate, leading to the mitigation of ASR expansion. Our findings underscore that larger aggregates retain a greater quantity of gels, resulting in more pronounced expansion. To establish an ASR prediction model based on the relationship of the ASR expansion of concrete to high and low temperatures, the parameters such as the range of curing temperatures and the grading size of aggregates should be carefully considered for the experiments.

Whole-Genome Sequencing Identified a Novel Mutation in the N-Terminal Domain of KIF5A in Chinese Patients with Familial Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive damage to both upper and lower motor neurons. Genetic factors are known to play a crucial role in ALS, as genetic studies not only advance our comprehension of disease mechanisms but also help unravel the complex phenotypes exhibited by patients. To gain further insights into the genetic landscape of ALS in the Chinese population and explore genotype-phenotype correlations among individuals, we conducted whole-genome sequencing to screen genes in 34 Chinese familial ALS (FALS) probands lacking the most common ALS-associated genes. Within this cohort, we identified a rare heterozygous missense mutation in the N-terminal domain of KIF5A (c.86A>G) in one of the probands. This finding is significant as mutations in the KIF5A gene have been implicated in ALS in European cohorts since 2018, predominantly characterized by C-terminal mutations. Analysis of the clinical phenotype within this familial lineage revealed a delayed onset of symptoms, an extended survival duration, and initial manifestations in both upper limbs. These observations underscore the clinical heterogeneity observed in ALS patients harboring KIF5A mutations. In conclusion, our study contributes to the growing body of evidence linking KIF5A to ALS and enhances our understanding of the intricate genetic landscape of this disease.

Cryopreservation-enhanced differentiation capacity of embryogenic cultures of Castanea mollissima.

A cryopreservation protocol has been developed for embryogenic cultures (ECs) of Castanea mollissima, an important economic species of the Castanea genus in China. We achieved 100 % regrowth when ECs were treated with Plant Vitrification Solution 2 (PVS2) for 30, 60 and 90 min on ice. Optimal PVS2 treatment for cryopreservation was determined to be 30 min on ice based on the highest biomass regrowth after thawing. Fluorescein diacetate (FDA) staining could rapidly and reliably determine post-thaw cell viability and its use facilitated the optimization of the cryopreservation protocols. Although the proliferation rate of the re-established ECs remained largely unchanged compared to non-cryopreserved ECs, the capacity of the re-established ECs to differentiate (on two media) into somatic embryos nearly doubled to approximately 2200-2300 globular somatic embryos per 1 g of re-established ECs. Based on cell cluster size analysis, this enhanced growth is primarily attributed to the presence of significantly greater cell clusters with a diameter of 100-200 µm, which have the highest level of differentiation ability. In order to understand the increased embryogenic potential following cryopreservation, we analyzed the expression of key genes related to somatic embryogenesis. Genes CmWUS and CmABP1 were downregulated while CmLEC1, CmAGL15, CmGRF2, and CmFUS3 were upregulated in re-established ECs when compared to non-cryopreserved ECs.

Analysis of Intracellular Communication Reveals Consistent Gene Changes Associated with Early-Stage Acne Skin.

A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS- 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.

Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient. METHODS/DESIGN: We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate. DISCUSSION: The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.

Improving Miscibility of Polymer Donor and Polymer Acceptor by Reducing Chain Entanglement for Realizing 18.64% Efficiency All Polymer Solar Cells.

All-polymer solar cells have experienced rapid development in recent years by the emergence of polymerized small molecular acceptors (PSMAs). However, the strong chain entanglements of polymer donors (PDs) and polymer acceptors (PAs) decrease the miscibility of the resulting polymer mixtures, making it challenging to optimize the blend morphology. Herein, we designed three PAs, namely PBTPICm-BDD, PBTPICγ-BDD and PBTPICF-BDD, by smartly using a BDD unit as the polymerized unit to copolymerize with different Y-typed non-fullerene small molecular acceptors (NF-SMAs), thus achieving a certain degree of distortion and giving the polymer system enough internal space to reduce the entanglements of the polymer chains. Such effects increase the chances of the PD being interspersed into the acceptor material, which improve the solubility between the PD and PA. The PBTPICγ-BDD and PBTPICF-BDD displayed better miscibility with PBQx-TCl, leading to a well optimized morphology. As a result, high power conversion efficiencies (PCEs) of 17.50% and 17.17% were achieved for PBQx-TCl:PBTPICγ-BDD and PBQx-TCl:PBTPICF-BDD devices, respectively. With the addition of PYF-T-o as the third component into PBQx-TCl:PBTPICγ-BDD blend to further extend the absorption spectral coverage and finely tune microstructures of the blend morphology, a remarkable PCE of 18.64% was realized finally.

Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Inflammation-associated intramyocellular lipid alterations in human pancreatic cancer cachexia.

BACKGROUND: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia. METHODS: Rectus abdominis muscle biopsies were collected during surgery of patients with pancreatic ductal adenocarcinoma (n = 10 without cachexia, n = 20 cachectic without inflammation (CRP < 10 mg/L), n = 10 cachectic with inflammation (CRP ≥ 10 mg/L). L3-CT scans were analysed to assess body composition based on validated thresholds in Hounsfield units (HU). Muscle sections were stained with Oil-Red O and H&E to assess general lipid accumulation and atrophy. Untargeted lipidomic analyses were performed on laser-microdissected myotubes using LC-MS/MS. The spatial distribution of intramyocellular lipids with differential abundance between groups was visualized by mass-spectrometry imaging. Genes coding for inflammation markers and enzymes involved in de novo ceramide synthesis were studied by qPCR. RESULTS: Muscle radiation attenuation was lower in cachectic patients with inflammation (median 24.3 [18.6-30.8] HU) as compared with those without inflammation (34.2 [29.3-38.7] HU, P = 0.033) or no cachexia (37.4 [33.9-42.9] HU, P = 0.012). Accordingly, intramyocellular lipid content was lower in non-cachectic patients (1.9 [1.6-2.1]%) as compared with those with cachexia with inflammation (5.5 [4.5-7.3]%, P = 0.002) or without inflammation (4.8 [2.6-6.0]%, P = 0.017). Intramyocellular lipid accumulation was associated with both local IL-6 mRNA levels (rs = 0.57, P = 0.015) and systemic CRP levels (rs = 0.49, P = 0.024). Compared with non-cachectic subjects, cachectic patients had a higher relative abundance of intramyocellular glycerophospholipids and a lower relative abundance of glycerolipids. Furthermore, increases in several intramyocellular lipids such as SM(d36:1), PC(34:1), and TG(48:1) were found in cachectic patients with inflammation and correlated with specific cachexia features. Altered intramyocellular lipid species such as PC(34:1), LPC(18:2), and TG(48:1) showed an uneven distribution in muscle sections of cachectic and non-cachectic patients, with areas featuring abundance of these lipids next to areas almost devoid of them. CONCLUSIONS: Intramyocellular lipid accumulation in patients with cachexia is associated with both local and systemic inflammation, and characterized by changes in defined lipid species such as glycerolipids and glycerophospholipids.

Chemokine receptor 7 contributes to T- and B-cell filtering in ageing bladder, cystitis and bladder cancer.

BACKGROUND: Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. METHODS: Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. RESULTS: Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P < 0.05). Three types of T-cells (NK T-cells, γδ T-cells and naïve T-cells) and three types of B-cells (follicular B-cells, plasma and memory B-cells) were identified in aged mice bladder. Chemokine receptor 7 (CCR7) is highly expressed in aged bladder, IC/BPS and BLCA (P < 0.05). CCR7 is likely to be involved in T- and B-cell infiltration in aged bladder, IC/BPS and BLCA. Interestingly, the high CCR7 expression on BLCA cell membranes was a prognostic protective factor. CONCLUSIONS: In this study, we characterised the expression profiles of immune cells in bladder tissues of aged and young mice and demonstrated that CCR7-mediated T- and B-cell filtration contributes to the development of bladder ageing, IC/BPS and BLCA.

Inhibition Studies of Expansion Damage in Medium-Low Reactivity Limestone by Fly Ash.

Expansion damage in medium-low reactivity dolomite limestone poses significant challenges in construction and engineering projects. This study investigates the potential of fly ash in inhibiting expansion damage in such limestone formations based on RILEM AAR-5 method. Through a series of laboratory experiments, various proportions of fly ash instead of cement, respectively, were prepared and subjected to varying alkali content conditions immersion tests to simulate expansion conditions. The expansion rates and extents were monitored and compared between pure limestone samples and those mixed with different proportions of fly ash. Additionally, scanning electron microscopy (SEM) analysis was employed to investigate the microstructure of the dolomite limestone-fly ash mixtures to understand the inhibition mechanisms. Results indicate that fly ash demonstrates promising inhibitory effects on expansion damage in medium-low reactivity dolomite limestone across the addition of 40% fly ash and alkali content of 0.70%. The reaction products are calcite, brucite, and a mixture of Mg-Si-Al phases and the reaction area is within 100 µm from the boundary when the cement alkali content is 1.50% without any fly ash. However, no reaction products were found at the boundary after adding 40% fly ash when lowering the cement alkali content to 0.70%. This research contributes to a better understanding of the interaction between fly ash and dolomite limestone in inhibiting expansion damage, providing valuable insights for engineering applications.