Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Comparative Analysis of Risk Factors and Dietary Status of High-risk Groups of Stroke in Urban and Rural Areas of Xiangtan City.

Objective: This study aimed to explore the risk factors and dietary status of middle-aged and elderly people at high risk of stroke in urban and rural areas of Xiangtan City, with a view to providing a basis for formulating stroke prevention and control strategies in urban and rural areas of Xiangtan City. Methods: Using the cluster sampling method, a total of 8,453 permanent residents aged ≥40 years old were selected from Yuetang Street, Yuetang District, and Jiangshe Town, Yuhu District, Xiangtan City in 2020 and 2021 for face-to-face questionnaire surveys to collect their demographic information, daily life Method, family history, height, weight, waist circumference, blood pressure, blood sugar, blood lipids, glycosylated hemoglobin, homocysteine and other indicators, and analyze them. Results: A total of 8453 permanent residents were screened in this study, and a total of 1804 stroke high-risk patients (including stroke and TIA, 21.34%) were screened out, including 973 urban residents (23.53%), and 831 rural residents (19.25%), and the distinction had statistical significance (P < .05); 263 stroke sufferers were screened out, and the prevalence ratio was 3.11%. The exposure rates of risk factors for high-risk groups in urban and rural areas of Xiangtan City from high to low are hypertension, dyslipidemia, smoking, family history of stroke, diabetes, obesity, lack of exercise and atrial fibrillation or heart valve disease. The high-risk groups for urban strokes The proportions of lack of exercise (23.54%) and obesity (38.44%) were significantly higher than the proportions of lack of exercise (17.09%) and obesity (22.64%) in rural areas. The high-risk groups in rural areas had hypertension (87.73%) and a history of TIA (2.89%). The proportion of patients with hypertension (82.43%) and TIA history (1.34%) was significantly higher than those in urban areas, and the differences were statistically significant (P < .05). The proportion of rural residents who eat a salty diet (17.93%) and eat fruits ≤2 days/week (93.98%) is significantly higher than that of urban residents who eat a salty diet (14.49%) and eat fruits ≤2 days/week (59.61%). There are differences. Statistically significant (P < .05), the proportion of urban residents who consume vegetables ≤2 days/week (11.91%) is significantly lower than the proportion of urban residents who consume vegetables ≤2 days/week (28.98%) (P < .01). Conclusion: The high-risk factors for stroke in Xiangtan City are mainly hypertension, dyslipidemia, smoking history, family history of stroke, and diabetes. Tailored public health measures should be taken by residents to address the different risk status and dietary habits of urban and rural populations. Especially dietary intervention for rural residents.

Causal relationships of lifestyle behaviours and body fat distribution on diabetic microvascular complications: a Mendelian randomization study.

Objectives: To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR). Methods: Genetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results. Results: There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58-2.33; p < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; p < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; p < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications. Conclusion: Our findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor.

Synergistic cytotoxicity and in vitro antioxidant activity of hederagenin and its glycoside from quinoa.

Although a series of studies confirm the bioactivities of hederagenin and its glycosides, their synergistic effects and potential mechanisms are still worthy of further exploration. This work investigated the synergistic cytotoxicity and in vitro antioxidant activity of hederagenin and hederagenin 28-O-ß-d-glucopyranoside (28-Glc-hederagenin). Hederagenin and 28-Glc-hederagenin inhibited HeLa cell growth and their combination further strengthened this effect. The combination of hederagenin and 28-Glc-hederagenin significantly increased the rate of apoptotic cells, suggesting the presence of a synergistic effect between the two substances. This combination also enhanced in vitro antioxidant activity compared with individual treatments. A network pharmacology and molecular docking-based approach was performed to explore the underlying mechanisms of hederagenin and 28-Glc-hederagenin against cervical cancer and oxidant damage. This work identified 18 related Kyoto Encyclopedia of Genes and Genome pathways, 202 related biological process terms, 17 related CC terms, and 35 related molecular function terms and then revealed 30 nodes and 196 edges. Subsequently, two highly connected clusters and the top four targets were identified. Molecular docking showed potent binding affinity of hederagenin and 28-Glc-hederagenin toward core targets associated with both cervical cancer and oxidant damage. This work may provide scientific basis for the combined use of hederagenin and its glycosides as dietary supplements.

Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering.

Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially and functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as a powerful tool to suppress the growth of existing tumors, as well as provide preventative efficacy against tumorigenesis. Delivering these vaccines more efficiently to LNs, where antigen-presenting cells (APCs) and T cells abundantly reside, is under extensive exploration. Formulating vaccines into nanomedicines, optimizing their physiochemical properties, and surface modification to specifically bind molecules expressed on LNs or APCs, are common routes and have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered to attract APCs and provide an environment for them to mature, proliferate and migrate to LNs. A relatively new research direction is inducing the formation of LN-like organoids, which have shown positive relevance to tumor prognosis. Cutting-edge advances in these directions and discussions from a future perspective are given here, from which the up-to-date pattern of cancer vaccination will be drawn to hopefully provide basic guidance to future studies.

Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection.

OBJECTIVE: Intracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. METHODS: This study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. RESULTS: The CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952-1.000), 0.973 (95 % CI 0.949-0.998), 0.884 (95 % CI 0.823-0.946), and 0.819 (95 % CI 0.733-0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989-1.000), which was higher than those of the four indicators alone. CONCLUSION: The combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.

Accelerating Intersystem Crossing in Multiresonance Thermally Activated Delayed Fluorescence Emitters via Long-Range Charge Transfer.

Multiresonance thermally activated delayed fluorescence (MR-TADF) emitters are excellent candidates for high-performance organic light-emitting diodes (OLEDs) due to their narrowband emission properties. However, the inherent mechanism of regulating the rate of intersystem crossing (ISC) is ambiguous in certain MR-TADF skeletons. Herein, we propose a mechanism of accelerating ISC in B/S-based MR-TADF emitters by peripheral modifications of electron-donating groups (EDGs) without affecting the narrowband emission property. The long-range charge transfer (LRCT) stems from the introduced EDG leading to high-lying singlet and triplet excited states. The ISC process is accelerated by the enhanced spin-orbital coupling (SOC) between the singlet short-range charge transfer (SRCT) and triplet LRCT manifolds. Meanwhile, the narrowband emission derived from the MR-type SRCT state is well retained as expected in the peripherally modified MR-TADF emitters. This work reveals the regulation mechanism of photophysical properties by high-lying LRCT excited states and provides a significant theoretical basis for modulating the rate of ISC in the further design of MR-TADF materials.

Medical knowledge graph completion via fusion of entity description and type information.

Medical Knowledge Graphs (MKGs) are vital in propelling big data technologies in healthcare and facilitating the realization of medical intelligence. However, large-scale MKGs often exhibit characteristics of data sparsity and missing facts. Following the latest advances, knowledge embedding addresses these problems by performing knowledge graph completion. Most knowledge embedding algorithms rely solely on triplet structural information, overlooking the rich information hidden within entity property sets, leading to bottlenecks in performance enhancement when dealing with the intricate relations of MKGs. Inspired by the semantic sensitivity and explicit type constraints unique to the medical domain, we propose BioBERT-based graph embedding model. This model represents an evolvable framework that integrates graph embedding, language embedding, and type information, thereby optimizing the utility of MKGs. Our study utilizes not only WordNet as a benchmark dataset but also incorporates MedicalKG to compare and corroborate the specificity of medical knowledge. Experimental results on these datasets indicate that the proposed fusion framework achieves state-of-art (SOTA) performance compared to other baselines. We believe that this incremental improvement provides promising insights for future medical knowledge graph completion endeavors.

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension.

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A-D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA-CREB-BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

Theoretical Study on the Reaction between Carcinogenic 2,5-Dichloro-1,4-benzoquinone and tert-Butyl Hydroperoxide: Self-Catalysis and Water Catalysis.

The potentially carcinogenic halobenzoquinones (HBQs) have been recently identified in drinking water as disinfection byproducts. Several radical intermediates in the reaction of 2,5-dichloro-1,4-benzoquinone (DCBQ) and t-butyl hydroperoxide (t-BuOOH), which may induce DNA damage, were detected experimentally, and metal-independent decomposition reactions of t-BuOOH by DCBQ were proposed. It has not yet been confirmed by theoretical calculations. The theoretical study in this work provides insights into the details of the reaction. An unprecedented self-catalysis mechanism of organic hydroperoxides, that is, the reactant t-BuOOH also has a catalytic effect, was uncovered at the molecular level. Moreover, as the solvent, water molecules also clearly have an efficient catalytic effect. Due to the catalysis of t-BuOOH and water, the metal-independent reaction of t-BuOOH and DCBQ can occur under moderate conditions. Our findings about the novel catalytic effect of organic hydroperoxides t-BuOOH could offer a unique perspective into the design of new catalysts and an understanding of the catalytic biological, environmental, and air pollution reactions. Furthermore, organic hydroperoxide t-BuOOH could serve as a proton shuttle, where the proton transfer process is accompanied by simultaneous charge transfer. Therefore, organic hydroperoxides may disrupt the vital proton transfer process in biological systems and may give rise to unexpected toxicity.

Chiral Recognition of Chiral (Hetero)Cyclic Derivatives Probed by Tetraaza Macrocyclic Chiral Solvating Agents via 1H NMR Spectroscopy.

In the field of chiral recognition, chiral cyclic organic compounds, especially heterocyclic organic compounds, have attracted little attention and have been rarely studied as chiral substrates by means of 1H NMR spectroscopy. In this paper, enantiomers of thiohydantoin derivatives, representing typical five-membered N,N-heterocycles, have been synthesized and utilized for assignment of absolute configuration and analysis of enantiomeric excess. All enantiomers have been successfully differentiated with the assistance of novel tetraaza macrocyclic chiral solvating agents (TAMCSAs) by 1H NMR spectroscopy. Surprisingly, unprecedented nonequivalent chemical shift values (up to 2.052 ppm) of the NH proton of substrates have been observed, a new milestone in the evaluation of enantiomers. To better understand the intermolecular interactions between host and guest, Job plots and theoretical calculations of (S)-G1 and (R)-G1 with TAMCSA 1a were investigated and revealed significant geometric differentiation between the diastereomers. In order to evaluate practical applications of the present systems in analyzing optical purity of chiral substrates, enantiomeric excesses of a typical substrate (G1) with different optical compositions in the presence of a representative TAMCSA (1a) can be accurately calculated based on the integration of the NH proton's signal peaks. Importantly, this work provides a significant breakthrough in exploring and developing the chiral recognition of chiral heterocyclic organic compounds by 1H NMR spectroscopy.

Reference intervals for cardiometabolic risk factors in China: a national multicenter cross-sectional study on an adult population sample.

Background: The reference intervals (RIs) of adult blood lipid parameters currently used in China are not derived from the results of research in local populations and have not been adjusted for age and sex. In this study, we aimed to determine accurate RIs for blood lipid parameters and blood glucose (GluG) for Chinese adults using a national multicenter study. Methods: A total of 11,333 adults between 18 and 90 years of age were recruited in seven representative regions in China between June 2020 and December 2020. Hospitals participating in the study were regrouped into two geographical regions, southern China (Changsha, Chengdu, Hangzhou, and Nanning) and northern China (Beijing, Shenyang, and Ningxia), according to their geographical and administrative location. All samples were freshly collected and measured collectively in one laboratory on the Mindray full Automatic biochemical analyzer chemistry BS2000 analytical systems. Outliers were removed using the Tukey test. Three-level nested analysis of variance and scatter plot were used to explore the variations in sex, age, and region. Percentile curves of each indicator were plotted using the least mean square (LMS) method. The lower limit (2.5th percentile) and the upper limit (97.5th percentile) of the RI were determined by using nonparametric statistical methods. We also calculated the 90% confidence interval (CI) for the lower and upper limits. Results: A total of 8,283 participants were enrolled in the final analysis, with 3,593 (43.4%) men and 4,690 (56.6%) women. Regionality was observed in three analytes [small dense low density lipoprotein cholesterol (sd-LDLC), GluG, and apolipoprotein A1 (ApoA1)]. In northern China, the sd-LDLC and GluG levels in Shenyang were significantly higher than those in Ningxia and Beijing (P<0.05). In southern China, the sd-LDLC and GluG levels in Nanning were significantly higher than those in the three other cities (P<0.05), whereas the sd-LDLC and GluG levels in Chengdu were significantly lower than those in the three other cities (P<0.05). The level of ApoA1 in Chengdu was significantly higher than that in the three other cities. The homocysteine (HCY) level in male participants was clearly higher than that in female participants [ratio of standard deviation (SDR)sex =0.56], whereas the levels of high density lipoprotein cholesterol (HDLC) (SDRsex =0.40) and ApoA1 (SDRsex =0.27) in males were lower. The GluG and HCY level increased gradually with age. In females aged 45-55 years, there was an interesting change in scatter charts, where triglyceride (TG) and total cholesterol (TC) increased rapidly. We also found that for the age group of >55 years, the levels of TG and TC in females gradually surpassed those in males. Conclusions: The findings of this study may help establish age- and sex-specific reference values for the blood lipids of Chinese adults and serve as a valuable guide for the screening, diagnosis, treatment, prevention, and monitoring of cardiovascular disease (CVD).

Non-cytochrome P450 enzyme aldehyde oxidase is involved in the oxidative metabolic pathway of diquat and its detoxification effect.

Diquat (DQ) poisoning has garnered attention in recent years, primarily due to the rising incidence of cases worldwide, coupled with the absence of a viable antidote for its treatment. Despite the fact that diquat monopyridone (DQ-M) has been identified as a significant metabolite of DQ, the enzyme responsible for its formation remains unknown. In this study, we have identified aldehyde oxidase (AOX) as a vital enzyme involved in DQ oxidative metabolism. The metabolism of DQ to DQ-M was significantly inhibited by AOX inhibitors including raloxifene and hydralazine. The source of oxygen incorporated into DQ-M was proved to be from water through a H218O incubation experiment which further corroborated DQ-M formation via AOX metabolism. The product of DQ-M in vitro generated by fresh rat tissues co-incubation was consistent with its AOX expression. The result of the molecular docking analysis of DQ and AOX protein showed that DQ is capable of binding to AOX. Furthermore, the cytotoxicity of DQ was significantly higher than DQ-M at the same concentration tested in six cell types. This work is the first to uncover the involvement of aldehyde oxidase, a non-cytochrome P450 enzyme, in the oxidative metabolic pathway of diquat, thus providing a potential target for the development of detoxification treatment.

Effect evaluation of competency-based education (CBE) combined with multi-disciplinary team (MDT) teaching mode in respiratory rehabilitation nursing teaching：A randomized controlled trial.

AIM: To explore the application effect of competency-based education (CBE) combined with multi-disciplinary team (MDT) teaching mode in respiratory rehabilitation nursing teaching. BACKGROUND: Respiratory rehabilitation, as an important non drug treatment for chronic respiratory disease, started late in China, with low implementation rate in hospitals and insufficient knowledge of nursing staff. Therefore, it is urgent to cultivate high professional level nurses with strong professional ability. DESIGN: A randomized controlled trial. METHODS: We selected nurses from the respiratory and critical care department at a Grade III, Level A hospital in Beijing, who participated in the respiratory rehabilitation training program between March 2020 and August 2022, as our study participants. Participants were grouped using a random number method. Nurses who participated in the study from March 2020 to May 2021 were set as the control group, and the nurses who participated in the study from June 2021 to August 2022 were set as the test group. The control group used traditional teaching methods, and the test group used the CBE combined MDT teaching model. At the end of the test, the theory, operating skills, satisfaction and core competence were assessed. RESULTS: After training, the theoretical examination score of the test group (93.71 ± 1.94) was higher than that of the control group (92.37 ± 1.92), the operational examination score of the test group (93.11 ± 2.12) was higher than that of the control group (91.61 ± 1.93), the overall teaching satisfaction of the test group (4.45 ± 0.50) was higher than that of the control group (4.13 ± 0.57), and the total score of the core competence of the test group (148.73 ± 7.08) was higher than that of the control group (141.02 ± 6.41). The difference between the two groups was statistically significant (P<0.05). CONCLUSION: CBE combined with MDT teaching mode has a good effect in Pulmonary and Critical Care Medicine (PCCM) respiratory rehabilitation nursing teaching.

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.

Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice.

BACKGROUND: IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs. METHODS: Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies. RESULTS: Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls. CONCLUSIONS: Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.

Efficiency of different imaging methods in detecting ocular foreign bodies.

BACKGROUND: Ocular foreign bodies (OFBs) are a relatively common occurrence in ocular injuries, and a severe risk factor for vision disorders. They are notoriously challenging to identify and localize precisely to allow surgical removal, even with the most recent technological advancements. PURPOSE: To compare the efficiency of different imaging methods in detecting and localizing OFBs. METHODS: We conducted a retrospective analysis of the medical records of patients with OFBs, detected by ultrasound biomicroscopy (UBM) and confirmed during surgery. Patients who presented to our medical center between January 2016 and January 2022 and also underwent computed tomography (CT), X ray, and/or ocular B-scan ultrasonography (B-scans) were selected. RESULTS: This study included 134 patients with a history of ocular trauma and OFBs (mean age: 47.25 years, range: 8-78). The mean time interval from injury to UBM examination was 36.31 months (range: 0.2-120 months). Most OFBs were metallic (51.82%) or plant-based (25.37%); 22.39% of them were located in the sclera, 26.87% in the anterior chamber, and 23.88% in the ciliary body and iris. OFBs ranged in size from 0.10 to 6.67 mm (mean: 1.15 ± 1.10 mm). B-scans identified OFBs in 37 of the 119 patients examined (31.09%); CT in 52 of 84 patients (61.90%); and radiography in 29 of 50 patients (58.00%). Univariate and multivariate analyses determined that both CT and radiography showed low detection rates for plant-based versus non-plant-based OFBs (CT: p < 0.001; radiography: p = 0.007), small particles (<1.00 mm vs. >1.00 mm; CT: p = 0.001, radiography: p = 0.024), and with eyeball wall locations (vs. intraocular; CT: p < 0.001, radiography: p = 0.021). Similarly, B-scans were less efficient for plant-based and eyeball wall-located OFBs (both p = 0.001), whereas the difference based on dimensions was not significant (p = 0.118). CONCLUSIONS: CT, radiography, and B-scans showed lower detection rates for plant-based, small, and eyeball wall-located OFBs. Our findings strongly suggest that UBM could be a more adequate imaging modality when such OFBs are suspected.

Polyoxometalate-Organic Hybrid "Calixarenes" as Supramolecular Hosts.

Calixarenes are among the most useful and versatile macrocycles in supramolecular chemistry. The one thing that has not changed in the 80 years since their discovery, despite numerous derivatizations, is their fully organic, covalent scaffolds. Here, we report a new type of organic-inorganic hybrid "calixarenes" constructed by means of coordination-driven assembly. Replacing acetate ligands on the {SiW10 Cr2 (OAc)2 } clusters with 5-hydroxyisophthalates allows these 95° inorganic building blocks to be linked into bowl-shaped, hybrid "calix[n]arenes" (n=3, 4). With a large concave cavity, the metal-organic calix[4]arene can accommodate nanometer-sized polyoxoanions in an entropically driven process. The development of hybrid variants of calixarenes is expected to expand the scope of their physicochemical properties, guest/substrate binding, and applications on multiple fronts.