Glycerol-driven adaptive evolution for the production of low-molecular-weight Welan gum: Characterization and activity evaluation.

Through adaptive laboratory evolution (ALE) of Sphingomonas sp. ATCC 31555, fermentation for production of low-molecular-weight welan gum (LMW-WG) was performed using glycerol as sole carbon source. During ALE, GPC-MALS analysis revealed a gradual decrease in WG molecular weight with the increase of adaptation cycles, accompanied by changes in solution conformation. LMW-WG was purified and structurally analyzed using GPC-MALS, monosaccharide composition analysis, infrared spectroscopy, NMR analysis, atomic force microscopy, and scanning electron microscopy. Subsequently, LMW-WG obtains hydration, transparency, antioxidant activity, and rheological properties. Finally, an in vitro simulation colon reactor was used to evaluate potential prebiotic properties of LMW-WG as dietary fiber. Compared with WG produced using sucrose as substrate, LMW-WG exhibited a fourfold reduction in molecular weight while maintaining moderate viscosity. Structurally, L-Rha nearly completely replaced L-Man. Furthermore, LMW-WG demonstrated excellent hydration, antioxidant activity, and high transparency. It also exhibited resistance to saliva and gastrointestinal digestion, showcasing a favorable colonization effect on Bifidobacterium, making it a promising symbiotic agent.

Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat.

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Intermittent hypoxia training enhances Aß endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer's disease.

BACKGROUND: Beta-amyloid (Aß) deposition in the brain parenchyma is a crucial initiating step in the amyloid cascade hypothesis of Alzheimer's disease (AD) pathology. Furthermore, dysfunction of plaque-associated microglia, also known as disease-associated microglia (DAM) has been reported to accelerate Aß deposition and cognitive impairment. Our previous research demonstrated that intermittent hypoxia training (IHT) improved AD pathology by upregulating autophagy in DAM, thereby enhancing oligomeric Aß (oAß) clearance. Considering that oAß internalization is the initial stage of oAß clearance, this study focused on the IHT mechanism involved in upregulating Aß uptake by DAM. METHODS: IHT was administered to 8-month-old APP/PS1 mice or 6-month-old microglial vacuolar protein sorting 35 (VPS35) knockout mice in APP/PS1 background (MG VPS35 KO: APP/PS1) for 28 days. After the IHT, the spatial learning-memory capacity of the mice was assessed. Additionally, AD pathology was determined by estimating the nerve fiber and synapse density, Aß plaque deposition, and Aß load in the brain. A model of Aß-exposed microglia was constructed and treated with IHT to explore the related mechanism. Finally, triggering receptor expressed on myeloid cells 2 (TREM2) intracellular recycling and Aß internalization were measured using a fluorescence tracing technique. RESULTS: Our results showed that IHT ameliorated cognitive function and Aß pathology. In particular, IHT enhanced Aß endocytosis by augmenting the intracellular transport function of microglial TREM2, thereby contributing to Aß clearance. Furthermore, IHT specifically upregulated VPS35 in DAM, the primary cause for the enhanced intracellular recycling of TREM2. IHT lost ameliorative effect on Aß pathology in MG VPS35 KO: APP/PS1 mice brain. Lastly, the IHT mechanism of VPS35 upregulation in DAM was mediated by the transcriptional regulation of VPS35 by transcription factor EB (TFEB). CONCLUSION: IHT enhances Aß endocytosis in DAM by upregulating VPS35-dependent TREM2 recycling, thereby facilitating oAß clearance and mitigation of Aß pathology. Moreover, the transcriptional regulation of VPS35 by TFEB demonstrates a close link between endocytosis and autophagy in microglia. Our study further elucidates the IHT mechanism in improving AD pathology and provides evidence supporting the potential application of IHT as a complementary therapy for AD.

Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review.

The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

To explore the impact of traumatic birth experiences on midwives' experience of empathy: A qualitative study.

OBJECTIVE: This study aimed to investigate the experiences of Chinese midwives during traumatic birth experiences and their impact. By doing so, we hope to develop effective empathetic educational strategies and provide valuable insights to improve the midwifery support system in China. METHODS: This study adopted Colaizzi's phenomenological approach, which aimed to understand and explore human experiences from the standpoint of the participants. A purposive sampling method was used to select 16 midwives for semi-structured interviews. The Colaizzi 7-step method was used to analyze the interview data. FINDINGS: Three themes and eight sub-themes were developed by analyzing and integrating the interview data. These included intertwined negative experiences (self-blame and guilt, regurgitated disturbances, intense and persistent physical and psychological discomfort, and low confidence in midwifery decision-making behaviours), the coexistence of positive effects (increased ability to tolerate life uncertainty, increased sense of control in coping with traumatic birth experiences), and needs and expectations (confiding in co-workers, an expectation of professional psychological support interventions). CONCLUSIONS: The experiences of midwives in showing empathy during traumatic birth experiences are complex and multifaceted. It is crucial to recognize and address negative empathic experiences, provide coping strategies, and enhance positive empathic experiences. Midwives' grief counselling competence education should be strengthened, as should their psychological well-being and the midwifery support system.

Artificial diets can manipulate the reproductive development status of predatory ladybird beetles and hold promise for their shelf-life management.

With the development of biological control methods, the predatory ladybird beetle Harmonia axyridis Pallas (Coleoptera: Coccinellidae) has been widely used for pest control in agricultural production. Appropriate shelf-life management strategies could synchronize H. axyridis production with pest outbreaks, finally improving the effectiveness of biological control. Herein, we preliminarily explored whether an artificial diet could optimize the shelf-life management of H. axyridis. We compared the survival rate, nutrition accumulation, reproductive development, juvenile hormone (JH) related-gene expression levels, and stress resistance gene expression levels between aphid-fed and artificial diet-fed H. axyridis females. The results revealed that H. axyridis females maintained a high survival rate after being fed an artificial diet for 60 days, whereas the survival rate of aphid-fed females decreased. Continuous feeding of the artificial diet caused H. axyridis females to enter a diapause-like state, which was characterized by low JH levels, high triglycerides and trehalose accumulation, ovarian development inhibition, decreased Vgs expression levels, and increased stress resistance gene expression levels. This diapause-like state could be promptly recovered upon transferring to an aphid diet. These results indicate that the artificial diet could manipulate the reproductive development status of H. axyridis and lay the foundation for its shelf-life management.

Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours.

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

Effect of crystal facets in plasmonic catalysis.

While the role of crystal facets is well known in traditional heterogeneous catalysis, this effect has not yet been thoroughly studied in plasmon-assisted catalysis, where attention has primarily focused on plasmon-derived mechanisms. Here, we investigate plasmon-assisted electrocatalytic CO2 reduction using different shapes of plasmonic Au nanoparticles - nanocube (NC), rhombic dodecahedron (RD), and octahedron (OC) - exposing {100}, {110}, and {111} facets, respectively. Upon plasmon excitation, Au OCs doubled CO Faradaic efficiency (FECO) and tripled CO partial current density (jCO) compared to a dark condition, with NCs also improving under illumination. In contrast, Au RDs maintained consistent performance irrespective of light exposure, suggesting minimal influence of light on the reaction. Temperature experiments ruled out heat as the main factor to explain such differences. Atomistic simulations and electromagnetic modeling revealed higher hot carrier abundance and electric field enhancement on Au OCs and NCs than RDs. These effects now dominate the reaction landscape over the crystal facets, thus shifting the reaction sites when comparing dark and plasmon-activated processes. Plasmon-assisted H2 evolution reaction experiments also support these findings. The dominance of low-coordinated sites over facets in plasmonic catalysis suggests key insights for designing efficient photocatalysts for energy conversion and carbon neutralization.

The clinical and pathological features of Kimura disease in pediatric patients.

Background: Kimura disease is characterized by inflammation, with its underlying causes remaining uncertain. There is a lack of comprehensive and systematic research on the pathology of this condition in pediatric patients. Our objective is to study the clinical and pathological attributes of Kimura disease in pediatric patients and investigate the potential diagnostic significance of immunoglobulin E (IgE) in this context. Methods: Clinical and laboratory information, pathological characteristics, and follow-up data were correlated to examine the distinctive features. Immunohistochemistry, acid-fast staining, and molecular assay were used to identify the presence of IgE and pathogens. Results: We conducted an analysis of five cases of Kimura disease in pediatric patients at our hospital. The patients' ages ranged from 5 years and 7 months to 14 years and 2 months, with 4 (80%) being male. The most common site was the head and neck region, particularly the postauricular subcutaneous area. Eosinophilia was observed in four patients (80%), and two patients (40%) had elevated serum immunoglobulin E (IgE) levels. Histopathological changes included eosinophilic infiltrates, follicular hyperplasia, and the proliferation of postcapillary venules. Immunohistochemical results supported the reactive nature of the lymphoid process and IgE deposition in the follicle, while no specific pathogens were discovered by special staining. All patients underwent surgical excision, and none experienced recurrence in their original location. Conclusion: Children with Kimura disease show distinct eosinophilic and IgE alterations in both laboratory findings and pathological features. The application of immunohistochemical staining of IgE could serve as a promising marker for diagnosing Kimura disease.

Life Satisfaction and Its Relationship With Personality Traits Among Medical College Students in China.

BACKGROUND: Life satisfaction is a comprehensive psychological index to measure a person's life quality. Previous studies have found that population sociological factors, physiological factors, psychological factors, and social factors all affect life satisfaction, but few studies have looked at the role of stable psychological factors, such as personality, in life satisfaction. Thus, this study combined previous research results and theories to study the current situation of college students' life satisfaction and its correlation with personality. OBJECTIVE: This study aims to comprehensively assess the life satisfaction levels among university students enrolled in a medical college in China, explore their correlation with various demographic factors and personality traits, identify potential areas for intervention, and provide recommendations for improving students' overall well-being and fostering the development of a positive and healthy personality. METHODS: A stratified cluster sampling method was used to select college students from a university. The questionnaire consists of general characteristics, a life satisfaction scale, and the Big Five Inventory. Descriptive statistical methods were conducted to describe the college students' life satisfaction status; an analysis of variance was performed to compare the score of life satisfaction among different demographic features; and the correlation between the score of life satisfaction and the Big Five Inventory was also analyzed. RESULTS: A total of 3116 subjects were included in this survey. The life satisfaction of females was higher than that of males in the dimensions of family, friends, school, and overall satisfaction (p<0.05). The life satisfaction of males in the self dimension was higher than that of females (p<0.05). The life satisfaction of different weight types had statistical significance in the life dimension (p<0.05). The life satisfaction of family, school, and overall well-being among smoking college students was lower than that of non-smoking college students (p<0.05). The life satisfaction of non-drinking college students in family, friends, life, school, and overall life satisfaction scores was higher than those of drinking college students (p<0.05). College students who get plenty of sleep a day (more than eight hours) scored higher life satisfaction scores in the self dimension than sleep-deprived college students (p<0.05). In addition to the family dimension, students taking long physical exercise breaks every day had higher life satisfaction scores in every dimension than students lacking physical exercise (p<0.05). The mean score of personality in the agreeableness and openness dimensions is the highest. Correlation analysis showed that the personality score in each dimension was positively correlated with the life satisfaction score in each dimension except for the neuroticism dimension of personality (p<0.05). CONCLUSION: The life satisfaction of college students is different for different lifestyles. The student management department should pay attention to the physical and mental health of college students with low life satisfaction and further find out the reasons for the difference in life satisfaction. Meanwhile, education should be strengthened for college students and encourage them to give up smoking and alcohol; strengthen physical training; and university education should strengthen the personality cultivation of college students.

DSFE: Decoding EEG-based finger motor imagery using feature-dependent frequency, feature fusion and ensemble learning.

Accurate decoding finger motor imagery is essential for fine motor control using EEG signals. However, decoding finger motor imagery is particularly challenging compared with ordinary motor imagery. This paper proposed a novel EEG decoding method of featuredependent frequency band selection, feature fusion, and ensemble learning (DSFE) for finger motor imagery. First, a feature-dependent frequency band selection method based on correlation coefficient (FDCC) was proposed to select feature-specific effective bands. Second, a feature fusion method was proposed to fuse different types of candidate features to produce multiple refined sets of decoding features. Finally, an ensemble model using the weighted voting strategy was proposed to make full use of these diverse sets of final features. The results on a public EEG dataset of five fingers motor imagery showed that the DSFE method is effective and achieves the highest decoding accuracy of 50.64%, which is 7.64% higher than existing studies using exactly the same data. The experiments further revealed that both the effective frequency bands of different subjects and the effective frequency bands of different types of features are different in finger motor imagery. Furthermore, compared with two-hand motor imagery, the effective decoding information of finger motor imagery is transferred to the lower frequency. The idea and findings in this paper provide a valuable perspective for understanding fine motor imagery in-depth.

Iron indices mediate but not modify association of parathyroid hormone with erythropoietin resistance in hemodialysis patients.

INTRODUCTION: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. METHODS: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr) and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the cor-relations of iron indices, PTH and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. RESULTS: The average ERI value of 10.3 ± 5.3 IU w-1 kg-1 (g/dL) -1. ERI was linked to PTH, hepcidin, CHr and TSAT (all P<0.05). PTH was associated with ERI levels (ß=0.007, 95%CI: 0.002-0.012, P=0.007). Hepcidin and PTH were closely correlated with each other (r = 0.28, P = 0.020). No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-fourth of the total association between PTH and ERI in hemodialysis population (25.71%, P=0.020). CONCLUSION: Iron indices and PTH levels were related to ERI values. Hepcidin ap-peared to be closely correlated to PTH and partly mediate the association between PTH and ERI in he-modialysis population.

Causal associations between sarcopenia-related traits and intervertebral disc degeneration: a two-sample mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. METHODS: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. RESULTS: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). CONCLUSION: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice.

Ficolin-A induces macrophage polarization to a novel pro-inflammatory phenotype distinct from classical M1.

BACKGROUND: Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. METHODS: We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. RESULTS: Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. CONCLUSION: Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

Short-term glycemic variability and intracranial atherosclerotic plaque stability assessed by high-resolution MR vessel wall imaging in type 2 diabetes mellitus.

OBJECTIVE: To investigate the relationship between short-term glycemic variability in patients with T2DM and the vulnerability of intracranial atherosclerotic plaques using HR-MR-VWI. MATERIALS AND METHODS: In total, 203 patients with acute ischemic stroke (AIS)/transient ischemia (TIA) combined with T2DM were enrolled. All of them underwent HR-MR-VWI during the period between July 2020 and July 2023. 203 patients were divided into groups with higher (1,5-AG≤ 30.7 µmol/L) and lower (1,5-AG> 30.7 µmol/L) short-term glycemic variability. Patients were also divided into the T1WI and non-T1WI hyperintensity groups. Associated factors(FBG, HbA1c, and 1,5-AG)for the T1WI hyperintensity were analyzed by binary logistic regression. We used the area under the curve (AUC), while the sensitivity and specificity were calculated at the optimal threshold. The Delong test was employed to compare the quality of the AUC of the predictors. RESULTS: The group with higher short-term glycemic variability had a higher incidence of the hyperintensity on T1WI, higher degree of enhancement, higher degree of stenosis and smaller lumen area (P < 0.05). The T1WI hyperintensity group had higher HbA1c levels, higher hemoglobin levels and lower 1,5-AG levels(P < 0.05). 1,5-AG (OR = 0.971, 95 % CI: 0.954∼0.988, P = 0.001), HbA1c (OR=1.305, 95 % CI: 1.065∼1.598, P = 0.01) and male sex (OR = 2.048, 95 % CI: 1.016∼4.128, P = 0.045)/(OR=2.102, 95 % CI: 1.058∼4.177, P = 0.034) were independent risk factors for the hyperintensity on T1WI. 1,5-AG demonstrated enhanced performance and yielded the highest AUC of the receiver operator characteristic curve (AUC = 0.726), with sensitivity and specificity values of 0.727 and 0.635 respectively. CONCLUSION: 1,5-AG, HbA1c and male sex are independent predictors of intracranial plaques with T1WI hyperintensity, the greater short-term glycemic variability, the higher incidence of vulnerable plaques.

Self-Healing Guar Gum-Based Nanocomposite Hydrogel Promotes Infected Wound Healing through Photothermal Antibacterial Therapy.

Preventing bacterial infections is a crucial aspect of wound healing. There is an urgent need for multifunctional biomaterials without antibiotics to promote wound healing. In this study, we fabricated a guar gum (GG)-based nanocomposite hydrogel, termed GBTF, which exhibited photothermal antibacterial therapy for infected wound healing. The GBTF hydrogel formed a cross-linked network through dynamic borate/diol interactions between GG and borax, thereby exhibiting simultaneously self-healing, adaptable, and injectable properties. Additionally, tannic acid (TA)/Fe3+ nanocomplexes (NCs) were incorporated into the hydrogel to confer photothermal antibacterial properties. Under the irradiation of an 808 nm near-infrared laser, the TA/Fe3+ NCs in the hydrogel could rapidly generate heat, leading to the disruption of bacterial cell membranes and subsequent bacterial eradication. Furthermore, the hydrogels exhibited good cytocompatibility and hemocompatibility, making them a precandidate for preclinical and clinical applications. Finally, they could significantly promote bacteria-infected wound healing by reducing bacterial viability, accelerating collagen deposition, and promoting epithelial remodeling. Therefore, the multifunctional GBTF hydrogel, which was composed entirely of natural substances including guar gum, borax, and polyphenol/ferric ion NCs, showed great potential for regenerating infected skin wounds in clinical applications.

CircSCNN1A inhibits the proliferation, migration and invasion of renal cell carcinoma cells by decreasing CLDN8 expression through miR-590-5p.

BACKGROUND: Increasing evidence suggests that circular RNA (circRNA) plays a regulatory role in the progression of renal cell carcinoma (RCC). However, the precise function and underlying mechanism of circSCNN1A in RCC progression still remain unclear. METHODS: The expression levels of circSCNN1A, microRNA-590-5p (miR-590-5p), claudin 8 (CLDN8), cyclin D1, matrix metalloprotein 2 (MMP2), MMP9, E-cadherin, N-cadherin and vimentin were detected by a quantitative real-time polymerase chain reaction and Western blotting analysis. Immunohistochemistry assay was performed to analyze the positive expression rate of CLDN8. Cell proliferation was investigated by cell colony formation, 5-Ethynyl-2'-deoxyuridine and DNA content quantitation assays. Cell migration and invasion were assessed by wound-healing and transwell invasion assays. Interactions among circSCNN1A, miR-590-5p and CLDN8 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft mouse model assay was conducted to verify the effect of circSCNN1A on tumor formation in vivo. RESULTS: CircSCNN1A and CLDN8 expression were significantly downregulated, while miR-590-5p was upregulated in both RCC tissues and cells. CircSCNN1A overexpression inhibited RCC cell proliferation, migration and invasion, accompanied by decreases of cyclin D1, MMP2, MMP9, N-cadherin and vimentin expression and an increase of E-cadherin expression. CircSCNN1A acted as a miR-590-5p sponge and regulated RCC cell processes by binding to miR-590-5p. CLDN8, a target gene of miR-590-5p, was involved in the regulation of the biological behaviors of RCC cells by miR-590-5p. In addition, circSCNN1A induced CLDN8 production by interacting with miR-590-5p. Further, circSCNN1A suppressed tumor formation in vivo. CONCLUSION: CircSCNN1A inhibited RCC cell proliferation, migration and invasion by regulating the miR-590-5p/CLDN8 pathway.

TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.