Breaking barriers: How modified citrus pectin inhibits galectin-8.

Inhibition of galectin-3-mediated interactions by modified citrus pectin (MCP) could affect several rate-limiting steps in cancer metastasis, but the ability of MCP to antagonize galectin-8 function remains unknown. We hypothesized that MCP could bind to galectin-8 in addition to galectin-3. In this study, a combination of gradual ethanol precipitation and DEAE-Sepharose Fast Flow chromatography was used to isolate several fractions from MCP. The ability of these fractions to antagonize galectin-8 function was studied as well as the primary structure and initial structure-function relationship of the major active component MCP-30-3. The results showed that MCP-30-3 (168 kDa) was composed of Gal (13.8%), GalA (63.1%), GlcA (13.0%), and Glc (10.1%). MCP-30-3 could specifically bind to galectin-8, with an MIC value of 0.04 mg mL-1. After MCP-30-3 was hydrolyzed by ß-galactosidase or pectinase, its binding activity was significantly reduced. These results provide new insights into the interaction between MCP structure and galectin function, as well as the potential utility in the development of functional foods.

PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia.

As a rate-limiting enzyme for the serine biosynthesis pathway (SSP) in the initial step, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in many different tumors, and pharmacological or genetic inhibition of PHGDH promotes antitumor effects. In the present research, by analyzing several acute myeloid leukemia (AML) datasets in the Gene Expression Omnibus (GEO), we identified prognosis-related genes and constructed a multigene signature by univariate, multivariate Cox regression and LASSO regression. Subsequently, the multigene signature was confirmed through Cox, Kaplan-Meier, and ROC analyses in the validation cohort. Moreover, PHGDH acted as a risk factor and was correlated with inferior overall survival. We further analysed other datasets and found that PHGDH was overexpressed in AML. Importantly, the expression of PHGDH was higher in drug-resistant AML compared to drug-sensitive ones. In vitro experiments showed that inhibition of PHGDH induced apoptosis and reduced proliferation in AML cells, and these antitumor effects could be related to the Bcl-2/Bax signaling pathway by the noncanonical or nonmetabolic functions of PHGDH. In summary, we constructed a twenty-gene signature that could predicate prognosis of AML patients and found that PHGDH may be a potential target for AML treatment.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Intracellular Zn2+ promotes extracellular matrix remodeling in dexamethasone-treated trabecular meshwork.

Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It is widely agreed that glucocorticoids impact the expression of matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIPs) and metallothionein. ZIP8 knockdown impaired extracellular Zn2+ uptake, but Zn2+ chelation did not affect ZIP8 expression. Resembling DEX's effects, chelation of Zn2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn2+ in DEX-treated cells ameliorated these outcomes. Notably, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.NEW & NOTEWORTHY Our study explores zinc's pivotal role in mitigating extracellular matrix dysregulation in the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that in human trabecular meshwork cells treated with dexamethasone, intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. Zinc supplementation rescues visual function by modulating extracellular matrix proteins and lowering intraocular pressure, offering a direction for further exploration in glaucoma management.

The rodent models of arteriovenous fistula.

Arteriovenous fistulas (AVFs) have long been used as dialysis access in patients with end-stage renal disease; however, their maturation and long-term patency still fall short of clinical needs. Rodent models are irreplaceable to facilitate the study of mechanisms and provide reliable insights into clinical problems. The ideal rodent AVF model recapitulates the major features and pathology of human disease as closely as possible, and pre-induction of the uremic milieu is an important addition to AVF failure studies. Herein, we review different surgical methods used so far to create AVF in rodents, including surgical suturing, needle puncture, and the cuff technique. We also summarize commonly used evaluations after AVF placement. The aim was to provide recent advances and ideas for better selection and induction of rodent AVF models. At the same time, further improvements in the models and a deeper understanding of AVF failure mechanisms are expected.

NanoSHP099-Targeted SHP2 Inhibition Boosts Ly6Clow Monocytes/Macrophages Differentiation to Accelerate Thrombolysis.

Tumor-associated thrombus (TAT) accounts for a high proportion of venous thromboembolism. Traditional thrombolysis and anticoagulation methods are not effective due to various complications and contraindications, which can easily lead to patients dying from TAT rather than the tumor itself. These clinical issues demonstrate the need to research diverse pathways for adjuvant thrombolysis in antitumor therapy. Previously, the phenotypic and functional transformation of monocytes/macrophages is widely reported to be involved in intratribal collagen regulation. This study finds that myeloid deficiency of the oncogene SHP2 sensitizes Ly6Clow monocyte/macrophage differentiation and can alleviate thrombus organization by increasing thrombolytic Matrix metalloproteinase (MMP) 2/9 activities. Moreover, pharmacologic inhibition by SHP099, examined in mouse lung metastatic tumor models, reduces tumor and thrombi burden in tumor metastatic lung tissues. Furthermore, SHP099 increases intrathrombus Ly6Clow monocyte/macrophage infiltration and exhibits thrombolytic function at high concentrations. To improve the thrombolytic effect of SHP099, NanoSHP099 is constructed to achieve the specific delivery of SHP099. NanoSHP099 is identified to be simultaneously enriched in tumor and thrombus foci, exerting dual tumor-suppression and thrombolysis effects. NanoSHP099 presents a superior thrombus dissolution effect than that of the same dosage of SHP099 because of the higher Ly6Clow monocyte/macrophage proportion and MMP2/MMP9 collagenolytic activities in organized thrombi.

KRT17 From Keratinocytes With High Glucose Stimulation Inhibit Dermal Fibroblasts Migration Through Integrin α11.

Objective: To investigate the effects of overexpressed keratin 17 (KRT17) on the biology of human dermal fibroblasts (HDFs) and to explore the mechanism of KRT17 in diabetic wound healing. Methods: KRT17 expression was tested in diabetic keratinocytes, animal models, and patient skin tissues (Huazhong University of Science and Technology Ethics Committee, [2022] No. 3110). Subsequently, HDFs were stimulated with different concentrations of KRT17 in vitro. Changes in the proliferation and migration of HDFs were observed. Then, identification of KRT17-induced changes in dermal fibroblast of RNA sequencing-based transcriptome analysis was performed. Results: KRT17 expression was upregulated under pathological conditions. In vitro stimulation of HDFs with different concentrations of KRT17 inhibited cell migration. RNA-seq data showed that enriched GO terms were extracellular matrix components and their regulation. KEGG analysis revealed that the highest number of enriched genes was PI3K-Akt, in which integrin alpha-11 (ITGA11) mRNA, a key molecule that regulates cell migration, was significantly downregulated. Decreased ITGA11 expression was observed after stimulation of HDFs with KRT17 in vitro. Conclusion: Increased expression of KRT17 in diabetic pathological surroundings inhibits fibroblast migration by downregulating the expression of ITGA11. Thus, KRT17 may be a molecular target for the treatment of diabetic wounds.

Acute caval thrombosis leading to obstructive shock in the early post insertion period of an inferior vena cava filter: a case report and literature review.

BACKGROUND: Obstructive shock is extremely rare in clinical practice and is caused by acute blood flow obstruction in the central vessels of either the systemic or pulmonary circulation. Utilizing inferior vena cava filters (IVCFs) to prevent pulmonary embolism (PE) is associated with some potential complications, such as inferior vena cava thrombosis (IVCT). Shock as a direct result of IVCT is rare. We present a case of obstructive shock secondary to extensive IVCT caused by inadequate anticoagulant therapy after the placement of an IVCF. CASE PRESENTATION: A 63-year-old male patient with a traffic accident injury presented orthopaedic trauma and lower limb deep vein thrombosis (DVT). He experienced sudden and severe abdominal pain with hypotension, tachycardia, tachypnea, oliguria and peripheral oedema 5 days after IVCF placement and 3 days after cessation of anticoagulant therapy. Considering that empirical anti-shock treatment lasted for a while and the curative effect was poor, we finally recognized the affected vessels and focused on the reason for obstructive shock through imaging findings-inferior vena cava thrombosis and occlusion. The shock state immediately resolved after thrombus aspiration. The same type of shock occurred again 6 days later during transfer from the ICU to general wards and the same treatment was administered. The patient recovered smoothly in the later stage, and the postoperative follow-up at 1, 3, and 12 months showed good results. CONCLUSION: This case alerts clinicians that it is crucial to ensure adequate anticoagulation therapy after IVCF placement, and when a patient presents with symptoms such as hypotension, tachycardia, and lower limb and scrotal oedema postoperatively, immediate consideration should be given to the possibility of obstructive shock, and prompt intervention should be based on the underlying cause.

Description and genomic characterization of Cohnella caldifontis sp. nov., isolated from hot springs in Yunnan province, south-west China.

A bacterial strain, Gram staining positive, strictly aerobic, rod-shaped, motile bacterium with flagellum and endospore-forming, designated strain YIM B05605T, was isolated from soil sampled in Hamazui hot springs, Tengchong City, Yunnan province, China. Optimum growth for the strain occurred at pH 7.0 and 45 °C. MK-7 was the main menaquinone in the strain YIM B05605T. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PME), unidentified glycolipid (GL), three unknown aminophospholipids (APLs) and unidentified polarlipid (PL) were part of the polar lipid profile. The major fatty acids were anteiso-C15:0 and iso-C16:0. The DNA G + C content of the type strain was 58.76%. Genome-based phylogenetic analysis confirmed that strain YIM B05605T formed a distinct phylogenetic cluster within the genus Cohnella. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of strain YIM B05605T with the most related species C. fontinalis YT-1101T were 73.42% and 15.7%. Functional analysis by NR, Swiss-prot, Pfam, eggNOG, GO, KEGG databases revealed that strain YIM B05605T has 13 genes related to the sulfur cycle, 2 genes related to the nitrogen cycle. Based on phylogenomic and phylogenetic analyses coupled with phenotypic and chemotaxonomic characterizations, strain YIM B05605T could be classified as a novel species of the genus Cohnella, for which the name Cohnella caldifontis sp. nov., is proposed. The type strain is YIM B05605T (= CGMCC 1.60052T = KCTC 43462T = NBRC 115921T).

Fractionation and antioxidation activities of polysaccharides from Zanthoxylum bungeanum Maxim.

Zanthoxylum bungeanum has a lengthy history of widespread use as a food ingredient in China. However, the composition of Zanthoxylum bungeanum polysaccharide remains ambiguous, and the antioxidant effect has received limited attention. This study aimed to extract water-soluble polysaccharide from the dried pericarp of Zanthoxylum bungeanum, referred to as WZBP, which was fractionated into a neutral component (WZBP-N) and three pectic components (WZBP-A-I, WZBP-A-II, WZBP-A-III). The findings indicated that WZBP-A-III is a pectic polysaccharide "smooth region" without many side chains. All components of WZBP exhibited a notable capacity for scavenging free radicals, with WZBP-A-III demonstrating the most potent antioxidation activity, and WZBP-A-III also observed to effectively extend the lifespan of Drosophila melanogaster and enhanced the activity of antioxidant enzymes. These results provide valuable insight and direction for future research on Zanthoxylum bungeanum polysaccharide as an antioxidant agent.

Global miRNA profiling reveals key molecules that contribute to different chronic lymphocytic leukemia incidences in Asian and Western populations.

It has been known for decades that the incidence of chronic lymphocytic leukemia (CLL) is significantly lower in Asia than in Western countries, but the reason responsible for this difference still remains a major knowledge gap. Using GeneChip® miRNA array to analyze the global microRNA expression in B lymphocytes from Asian and Western CLL patients and healthy individuals, we have identified microRNA with CLL-promoting or suppressive functions that are differentially expressed in Asian and Western individuals. In particular, miR-4485 is upregulated in CLL patients of both ethnic groups, and its expression is significantly lower in Asian healthy individuals. Genetic silencing of miR-4485 in CLL cells suppresses leukemia cell growth, whereas ectopic expression of miR-4485 promotes cell proliferation. Mechanistically, miR-4485 exerts its CLL-promoting activity by inhibiting the expression of TGR5 and activating the ERK1/2 pathway. In contrast, miR-138, miR-181a, miR- 181c, miR-181d, and miR-363 with tumor-suppressive function are highly expressed in Asian healthy individuals. Our study suggests that differential expression of several important microRNA with pro- or anti-CLL functions in Asian and Western B lymphocytes likely contributes to the difference in CLL incidence between the two ethnic groups, and that miR-4485 and its downstream molecule TGR5 could be potential therapeutic targets.

Navigation Learning Assessment Using EEG-Based Multi-Time Scale Spatiotemporal Compound Model.

This study presents a novel method to assess the learning effectiveness using Electroencephalography (EEG)-based deep learning model. It is difficult to assess the learning effectiveness of professional courses in cultivating students' ability objectively by questionnaire or other assessment methods. Research in the field of brain has shown that innovation ability can be reflected from cognitive ability which can be embodied by EEG signal features. Three navigation tasks of increasing cognitive difficulty were designed and a total of 41 subjects participated in the experiment. For the classification and tracking of the subjects' EEG signals, a convolutional neural network (CNN)-based Multi-Time Scale Spatiotemporal Compound Model (MTSC) is proposed in this paper to extract and classify the features of the subjects' EEG signals. Furthermore, Spiking neural networks (SNN) -based NeuCube is used to assess the learning effectiveness and demonstrate cognitive processes, acknowledging that NeuCube is an excellent method to display the spatiotemporal differences between spikes emitted by neurons. The results of the classification experiment show that the cognitive training traces of different students in solving three navigational problems can be effectively distinguished. More importantly, new information about navigation is revealed through the analysis of feature vector visualization and model dynamics. This work provides a foundation for future research on cognitive navigation and the training of students' navigational skills.

Reduced Zn2+ promotes retinal ganglion cells survival and optic nerve regeneration after injury through inhibiting autophagy mediated by ROS/Nrf2.

The molecular mechanism of how reduced mobile zinc (Zn2+) affected retinal ganglion cell (RGC) survival and optic nerve regeneration after optic nerve crush (ONC) injury remains unclear. Here, we used conditionally knocked out ZnT-3 in the amacrine cells (ACs) of mice (CKO) in order to explore the role of reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) and autophagy in the protection of RGCs and axon regeneration after ONC injury. We found that reduced Zn2+ can promote RGC survival and axonal regeneration by decreasing ROS, activating Nrf2, and inhibiting autophagy. Additionally, autophagy after ONC is regulated by ROS and Nrf2. Visual function in mice after ONC injury was partially recovered through the reduction of Zn2+, achieved by using a Zn2+ specific chelator N,N,N',N'-tetrakis-(2-Pyridylmethyl) ethylenediamine (TPEN) or through CKO mice. Overall, our data reveal the crosstalk between Zn2+, ROS, Nrf2 and autophagy following ONC injury. This study verified that TPEN or knocking out ZnT-3 in ACs is a promising therapeutic option for the treatment of optic nerve damage and elucidated the postsynaptic molecular mechanism of Zn2+-triggered damage to RGCs after ONC injury.

Posttraumatic arteriovenous fistula of the lower extremity and the pathological characteristic-case series and literature review.

The clinical presentation, treatment history, and outcomes of two patients with posttraumatic arteriovenous fistula (PTAVF) were analyzed and compared with the pathological tissues of patients with hemodialysis arteriovenous fistula (HAVF). A search of the biomedical literature database (PubMed), using the keywords " lower extremity" and "PTAVF," was conducted to obtain results and review the data. Postoperative histological analysis of patients with PTAVF showed differences from that of HAVF. The literature screening and analysis revealed that PTAVF is a chronic progressive process, with 70% of patients diagnosed after 3 months. The choice of treatment revealed that 20% of patients had severe complications and all were treated endovascularly. Due to the abnormal fistula of PTAVF and its specific histopathological features, the disease is not self-limiting. It is unwise to wait for PTAVF to cause "failure." We recommend early and timely cure of this disease by surgery to avoid serious complications.

Comparative bioinformatics analysis of transcriptomes between ß-aminopropionitrile-induced aortic dissection murine model and human aortic dissection.

Background: Aortic dissection (AD) poses a great threat to the life of patients; however, there is currently no documentation of a clear pathogenic mechanism of this disease. In recent years, ß-aminopropionitrile (BAPN)-induced AD in rodents has been widely used in basic research, which provides a good platform for exploring the pathogenesis of AD and drug modification. This study aimed to identify molecular markers and pathways for the diagnosis and treatment of AD by comparing a murine AD model and human AD transcriptome through a bioinformatics analysis. Methods: We constructed a BAPN-induced mice model and performed high-throughput sequencing analysis. The GSE147026 dataset of patients was obtained from the Gene Expression Omnibus database. We performed a subsequent bioinformatics analysis of human AD and the murine AD model using R software. The DESeq software package was used to analyze the differentially expressed genes (DEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to analyze the enrichment pathways. Protein-protein interaction network construction and hub gene selection were based on STRING software analysis. Stepwise identification of potential drugs was performed online, while hub genes were validated immunohistochemically. Results: We compared the murine AD model and human AD transcriptome and found that both differentially expressed 463 genes. The cytokine-cytokine receptor interaction, tuberculosis, and phagosome pathways were significantly enriched. CDC20, CCNB2, and CCNB1 may be associated with AD development. Protein-drug interactions were also identified. Conclusions: This study is the first to reveal transcriptional changes in a murine BAPN-induced AD model versus human AD transcriptome. Furthermore, we identified the important hub genes, related pathways, and potential drugs by analyzing the overlapping DEGs between human AD and the murine AD model. Our results provide a basis for the further identification of potential molecular markers for diagnosing and treating AD.

Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy.

OBJECTIVE: This study aimed to investigate the safety and efficacy of endovascular aortic repair (EVAR) for the treatment of an abdominal aortic aneurysm (AAA) with a hostile neck anatomy (HNA). METHODS: From January 1, 2015 to December 31, 2019, a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study. Based on the morphological characteristics of the proximal neck anatomy, the patients were divided into the HNA group and the friendly neck anatomy (FNA) group. The patients were followed up for up to 4 years. RESULTS: The average follow-up time was 1056.1±535.5 days. Type I endoleak occurred in 4 patients in the HNA group, and 2 patients in the FNA group. Neither death nor intraoperative switch to open repair occurred in either group. The time of the operation was significantly longer in the HNA group (FNA vs. HNA, 99.2±51.1 min vs. 117.5±63.8 min, P=0.011). There were no significant differences in short-term clinical success rate (P=0.228) or midterm clinical success rate (P=0.889) between the two groups. The overall mortality rate was 10.4%, and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period (P=0.889). CONCLUSION: EVAR was feasible and safe in patients with an AAA with a proximal HNA. The early and midterm results were promising; however, further studies are needed to verify the long-term effectiveness of EVAR.

Eye Movement Abnormalities During Different Periods in Patients with Vestibular Migraine.

Purpose: The aim of this study was to assess abnormal eye movement signs during different periods, namely, ictal periods and symptom-free intervals, in patients with vestibular migraine. Patients and Methods: We assessed oculomotor signs using videonystagmography in 90 patients with VM (40 during ictal periods and 50 during symptom-free intervals) according to validated diagnostic criteria. Results: Abnormal saccades, smooth pursuit and optokinetic test results; spontaneous nystagmus; and positional nystagmus were all observed in vestibular migraine patients, and there was no significant difference between different periods. Positional nystagmus was the most common in both the ictal and asymptomatic periods (60% and 36%, respectively). Positional nystagmus was induced in a variety of positions during both periods, and the slow-phase velocity ranged from <2 to 10°/s. The duration of positional nystagmus was over 60s in most cases. Overall, central oculomotor dysfunctions occurred in 27.5% of patients during VM attacks and 4% of patients during symptom-free intervals; this difference was statistically significant (p = 0.002). Conclusion: In patients with VM, abnormal oculomotor signs can be found during both vertigo attacks and asymptomatic intervals. Positional nystagmus is the most common of these abnormalities and can be induced in different positions. The amplitude of these patients' positional nystagmus tends to be low, and the duration tends to be long. Observing changes in eye movements by videonystagmography may be helpful in the diagnosis of VM.

PKCδ regulates the vascular biology in diabetic atherosclerosis.

Diabetes mellitus, known for its complications, especially vascular complications, is becoming a globally serious social problem. Atherosclerosis has been recognized as a common vascular complication mechanism in diabetes. The diacylglycerol (DAG)-protein kinase C (PKC) pathway plays an important role in atherosclerosis. PKCs can be divided into three subgroups: conventional PKCs (cPKCs), novel PKCs (nPKCs), and atypical PKCs (aPKCs). The aim of this review is to provide a comprehensive overview of the role of the PKCδ pathway, an isoform of nPKC, in regulating the function of endothelial cells, vascular smooth muscle cells, and macrophages in diabetic atherosclerosis. In addition, potential therapeutic targets regarding the PKCδ pathway are summarized. Video Abstract.