Lactiplantibacillus plantarum P9 for chronic diarrhea in young adults: a large double-blind, randomized, placebo-controlled trial.

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

A Reconfigurable Soft Helical Actuator with Variable Stiffness Skeleton.

Due to their exceptional adaptability, inherent compliance, and high flexibility, soft actuators have significant advantages over traditional rigid actuators in human-machine interaction and in grasping irregular or fragile objects. Most existing soft actuators are designed using preprogramming methods, which schedule complex motions into flexible structures by correctly designing deformation constraints. These constraints restrict undesired deformation, allowing the actuator to achieve the preprogrammed motion when stimulated. Therefore, these actuators can only achieve a certain type of motion, such as extension, bending, or twisting, since it is impossible to adjust the deformation constraints once they are embedded into the structures. In this study, we propose the use of variable stiffness materials, such as shape memory polymer (SMP), in the structural design of soft actuators to achieve variable stiffness constraints. A reconfigurable soft helical actuator with a variable stiffness skeleton is developed based on this concept. The skeleton, made of SMP, is encased at the bottom of a fiber-reinforced chamber. In its high-stiffness state, the SMP constrains the deformation toward the skeleton when the actuator is pressurized. This constraint is removed once the SMP skeleton is heated, endowing the actuator with the ability to switch between bending and helical motion in real-time. A theoretical model is proposed to predict the behavior of the actuator when driven by pressure, and experiments are conducted to verify the model's accuracy. In addition, the influence of different design parameters is investigated based on experimental results, providing reference guidelines for the design of the actuator.

Characterization of a novel mitophagy-related 5-genes signature for diagnosis of acute myocardial infarction.

Myocardial infarction (MI) and the ensuing heart failure (HF) remain the main cause of morbidity and mortality worldwide. One of the strategies to combat MI and HF lies in the ability to accurately predict the onset of these disorders. Alterations in mitochondrial homeostasis have been reported to be involved in the pathogenesis of various cardiovascular diseases (CVDs). In this regard, perturbations to mitochondrial dynamics leading to impaired clearance of dysfunctional mitochondria have been previously established to be a crucial trigger for MI/HF. In this study, we found that MI patients could be classified into three clusters based on the expression levels of mitophagy-related genes and consensus clustering. We identified a mitophagy-related diagnostic 5-genes signature for MI using support vector machines-Recursive Feature Elimination (SVM-RFE) and random forest, with the area under the ROC curve (AUC) value of the predictive model at 0.813. Additionally, the single-cell transcriptome and pseudo-time analyses showed that the mitoscore was significantly upregulated in macrophages, endothelial cells, pericytes, fibroblasts and monocytes in patients with ischemic cardiomyopathy, while sequestosome 1 (SQSTM1) exhibited remarkable increase in the infarcted (ICM) and non-infarcted (ICMN) myocardium samples dissected from the left ventricle compared with control samples. Lastly, through analysis of peripheral blood from MI patients, we found that the expression of SQSTM1 is positively correlated with troponin-T (P < 0.0001, R = 0.4195, R2 = 0.1759). Therefore, this study provides the rationale for a cell-specific mitophagy-related gene signature as an additional supporting diagnostic for CVDs.

Development and validation of a nomogram for cerebral hemorrhage in patients with carotid stenosis undergoing stenting: a multicenter retrospective study.

BACKGROUND: Hyperperfusion-induced cerebral hemorrhage (HICH) is a rare but severe complication in patients with carotid stenosis undergoing stent placement for which predictive models are lacking. Our objective was to develop a nomogram to predict such risk. METHODS: We included a total of 1226 patients with carotid stenosis who underwent stenting between June 2015 and December 2022 from three medical centers, divided into a development cohort of 883 patients and a validation cohort of 343 patients. The model used LASSO regression for feature optimization and multivariable logistic regression to develop the predictive model. Model accuracy was assessed via the receiver operating characteristic curve, with further evaluation of calibration and clinical utility through calibration curves and decision curve analysis (DCA). The model underwent internal validation using bootstrapping and external validation with the validation cohort. RESULTS: Older age (OR 1.07, p=0.005), higher degrees of carotid stenosis (OR 1.07, p=0.006), poor collateral circulation (OR 6.26, p<0.001), elevated preoperative triglyceride levels (OR 1.27, p=0.041) and neutrophil counts (OR 1.36, p<0.001) were identified as independent risk factors for HICH during hospitalization. The nomogram constructed based on these predictive factors demonstrated an area under the curve (AUC) of 0.817. The AUCs for internal and external validation were 0.809 and 0.783, respectively. Calibration curves indicated good model fit, and DCA confirmed substantial clinical net benefit in both cohorts. CONCLUSION: We developed and validated a nomogram to predict HICH in patients with carotid stenosis post-stenting, facilitating early identification and preventive intervention in high-risk individuals.

A Functionalized Scaffold Facilitates Neurites Extension for Spinal Cord Injury Therapy.

Scaffolds have garnered considerable attention for enhancing neural repairment for spinal cord injury (SCI) treatment. Both microstructural features and biochemical modifications play pivotal roles in influencing the interaction of cells with the scaffold, thereby affecting tissue regeneration. Here, a scaffold is designed with spiral structure and gradient peptide modification (GS) specifically for SCI treatment. The spiral structure provides crucial support and space, while the gradient peptide isoleucine-lysine-valine-alanine-valine (IKVAV) modification imparts directional guidance for neuronal and axonal extension. GS scaffold shows a significant nerve extension induction effect through its interlayer gap and gradient peptide density to dorsal root ganglia in vitro, while in vivo studies reveal its substantial promotion for functional recovery and neural repair. Additionally, the GS scaffold displays impressive drug-loading capacity, mesenchymal stem cell-derived exosomes can be efficiently loaded into the GS scaffold and delivered to the injury site, thereby synergistically promoting SCI repair. Overall, the GS scaffold can serve as a versatile platform and present a promising multifunctional approach for SCI treatment.

Long non-coding RNA SIX1-1 promotes proliferation of cervical cancer cells via negative transcriptional regulation of RASD1.

Cervical cancer poses a significant health burden for women globally, and the rapid proliferation of cervical cancer cells greatly worsens patient prognosis. Long non-coding RNAs (lncRNAs) play a crucial role in regulating tumor cell proliferation. However, the involvement of lncRNAs in cervical cancer cell proliferation remains unclear. In this study, we investigated the lncRNA SIX1-1, which was found to be upregulated in cervical cancer tissues and cell lines. Functional assays revealed that knockdown of SIX1-1 inhibited cell proliferation in vitro and reduced tumor growth in vivo. Mechanistically, SIX1-1 was predominantly localized in the nucleus and could bind with DNMT1 protein. The expression of SIX1-1 enhanced the interaction of DNMT1 with RASD1 promoter, leading to the methylation of the promoter and decreased mRNA transcription. Then RASD1 downregulation activated the cAMP/PKA/CREB signaling pathway, promoting cell proliferation. Rescue experiments showed that knockdown of RASD1 restored the inhibited cell proliferation caused by decreased expression of SIX1-1, indicating that RASD1 acted as the functional mediator of SIX1-1. In conclusion, SIX1-1 promoted cervical cancer cell proliferation by modulating RASD1 expression. This suggests that targeting the SIX1-1/RASD1 axis could be a potential antitumor strategy for cervical cancer.

Associations between dietary iron intake from different sources and non-alcoholic fatty liver disease in adults.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has become a worldwide public health problem. Current evidence on the association between dietary iron intake and the risk of NAFLD is limited. The present study aimed to investigate the associations of animal-derived dietary iron (ADDI) intake, plant-derived dietary iron (PDDI) intake, and the ratio of PDDI:ADDI with NAFLD risk among U.S. adult population. METHODS AND STUDY DESIGN: This was a repeated cross-sectional study. Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. NAFLD was defined as a United States Fatty Lives Index ≥30, and dietary iron intake was assessed through two 24-h dietary recall in-terviews. Logistic regression and restricted cubic spline models were applied to examine the associations between dietary iron intake from different sources and NAFLD risk. RESULTS: A total of 9478 participants aged ≥20 years were enrolled in the present study. After adjustment for multiple confounding factors, relative to the lowest quartile, the odds ratio (OR) and 95% confidence interval (CI) of NAFLD for the highest quartile was 1.01(95% CI, 0.82-1.24) for ADDI intake, 0.82 (95% CI, 0.64-0.99) for PDDI intake, and 1.00 (95% CI, 0.81-1.24) for the PDDI: ADDI intake ratio. In stratified analysis by sex and age, the significantly negative associations of PDDI intake with NAFLD was observed in women and participants older than 45 years. Dose-response analyses indicated that NAFLD was negatively associated with PDDI intake in a non-linear manner. CONCLUSIONS: PDDI intake was negatively associated with NAFLD in U.S. adults.

miR-590-3p Overexpression Improves the Efficacy of hiPSC-CMs for Myocardial Repair.

Recent evidence demonstrates that low engraftment rates limit the efficacy of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac repair after myocardial infarction. In this study, we attempted to overcome this limitation by enhancing the proliferative capacity of transplanted hiPSC-CMs. We found that miR-590-3p overexpression increased the proliferative capacity of hiPSC-CMs. miR-590-3p overexpression increased the number of engrafted cells and had a higher efficacy for myocardial repair than control cells. Moreover, we confirmed the safety of using miR-590-3p-overexpressing hiPSC-CMs in pig hearts. These results indicated that miR-590-3p overexpression stimulated hiPSC-CM cell cycle re-entry to induce cell proliferation and increased the therapeutic efficacy in MI.

Expose to volatile organic compounds is associated with increased risk of depression: A cross-sectional study.

With increasing prevalence rate of depression by years, more attention has been paid to the influence of environmental pollutants on depression, but relationship between exposure to volatile organic compounds (VOCs) and depression is rarely studied. Therefore, this cross-sectional study use the National Center for Health Statistics (NHANES) database (2013-2016 years) to explore association between exposure to multiple VOCs and depression in general population. Multiple linear and logistic regression models were used to analyze the association between urinary VOC metabolism (mVOCs) and depression. To further analyze effect of multiple mVOCs mixed exposure, Bayesian kernel machine regression (BKMR) models were performed. A total of 3240 participants and 16 mVOCs were included in the analysis. Results showed that 10 mVOCs exposure were positively correlated with depression by multiple linear and logistic regression models, especially CYMA and MHBMA3, which also showed significant positive association with depression in BKMR model. Mixed exposure of multiple mVOCs was significantly positively correlated with depression. Gender differences were existed in effects of some VOCs concentrations on depression. AAMA, CYMA and MA had significant positive correlations with depression by women, and DHBMA had significant positive correlations with depression by men. Hence, this study showed that exposing to VOCs might have negative impacts on depression, and impact of CYMA and MHBMA3 on depression may be more evident, which provide new ideas for prevention and control of depression. But further research and exploration are needed to clarify the mechanism and influence factors of this relationship, to demonstrate the reliability of these relationship.

Enhanced aerosol-jet printing using annular acoustic field for high resolution and minimal overspray.

Aerosol jet printing has the potential to fabricate fine features on various substrates due to its large stand-off distance. However, the presence of overspray and instability, particularly at high printing resolutions, has limited its widespread application. In this study, we introduce an efficient approach called annular acoustic focusing for aerosol jet printing. By determining the optimal focusing frequency (5.8 MHz) for silver nanoparticles using a particle ejection model, we achieve precise and stable printing. We also propose a modified print nozzle geometry, resulting in ultrafine traces (line width < 6 µm, overspray < 0.1 µm). Compared to printing without acoustic focusing, the line width of the traces decreases to 60 ± 5% while their conductivity increases to 180 ± 5%. Additionally, several 8 h experiments demonstrate excellent printing stability. This research opens up possibilities for the fabrication of conformal electronics with high precision and improved conductivity using aerosol jet printing.

Evaluation of fragility fracture risk using deep learning based on ultrasound radio frequency signal.

BACKGROUND: It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. AIMS: To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). METHODS: Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. RESULTS: Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). CONCLUSIONS: This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

The Gene Rearrangement and Transcriptional Regulation of Non B Cell-Derived Immunoglobulin.

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.

Shotgun metagenomic analysis of microbiota dynamics during long-term backslopping fermentation of traditional fermented milk in a controlled laboratory environment.

Traditional fermented milks are produced through an inoculation process that involves the deliberate introduction of microorganisms that have been adapted and perpetuated across successive generations. However, the changes in the microbiota of traditional fermented milk during long-term inoculation fermentation in a laboratory environment remain unclear. In this study, we collected 5 samples of traditional fermented milk samples from 5 different counties in Tibet (3 kurut products) and Xinjiang (2 tarag products) of China, which served as starter cultures for a 9-mo continuous inoculation fermentation experiment. We analyzed the inter- and intra-population variations in the microbial communities of the collected samples, representing their macrodiversity and microdiversity, using shotgun metagenomic sequencing. Across all samples, we obtained a total of 186 high-quality metagenomic-assembled genomes, including 7 genera and 13 species with a relative abundance of more than 1%. The majority of these genomes were annotated as Lactobacillus helveticus (60.46%), Enterococcus durans (9.52%), and Limosilactobacillus fermentum (6.23%). We observed significant differences in species composition and abundance among the 5 initial inoculants. During the long-term inoculation fermentation, we found an overall increasing trend in species diversity, composition, and abundances of carbohydrate metabolism module-encoding genes in the fermented milk bacterial metagenome, while the fermented milk virome exhibited a relatively narrow range of variation. Lactobacillus helveticus, a dominant species in traditional fermented milk, displayed high stability during the long-term inoculation fermentation. Our study provides valuable insights for the industrial production of traditional fermented milk.

IL-4 attenuates myocardial infarction injury by promoting M2 macrophage polarization.

IL-4, an immunoregulatory cytokine, plays a role in various cellular pathways and is known to regulate M2 macrophage polarization. Numerous studies have suggested that promoting the polarization of macrophages toward the M2 phenotype is beneficial for myocardial infarction (MI) recovery. However, whether IL-4 can achieve therapeutic effects in MI by regulating M2 macrophage polarization remains unclear. In this study, the authors observed that IL-4 increased the proportion of M2 macrophages in the ischemic myocardium compared to the PBS group. Additionally, IL-4 reduced the infiltration of inflammatory cells and the expression of proinflammatory-related proteins, while enhancing the expression of genes associated with tissue repair. Furthermore, IL-4 facilitated the recovery of cardiac function and reduced fibrosis in the post-MI phase. Importantly, when macrophages were depleted, the therapeutic benefits of IL-4 mentioned above were attenuated. These findings provide evidence for the effectiveness of IL-4 in treating MI through the regulation of M2 macrophage polarization, thereby encouraging further development of this therapeutic approach.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders.

AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P<0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio (P<0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy (P<0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy (P>0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Analysis of clinical characteristics of different types of lung function impaiement in TDL patients.

AIM: The clinical characteristics associated with pulmonary function decline in patients with Tuberculosis-destroyed lung (TDL) remain uncertain. We categorize them based on the pattern of pulmonary function impairment, distinguishing between restrictive spirometric pattern (RSP) and obstructive spirometric pattern (OSP). We aim to compare the severity of these patterns with the clinical characteristics of TDL patients and analyze their correlation. METHOD: We conducted a retrospective analysis on the clinical data of TDL patients who underwent consecutive pulmonary function tests (PFT) from November 2002 to February 2023. We used the lower limit formula for normal values based on the 2012 Global Lung Function Initiative. We compared the clinical characteristics of RSP patients with those of OSP patients. The characteristics of RSP patients were analyzed using the tertiles of forced vital capacity percentage predicted (FVC% pred) decline based on PFT measurements, and the characteristics of OSP patients were analyzed using the tertiles of forced expiratory volume in 1 s percentage predicted (FEV1% pred) decline. RESULT: Among the RSP patients, those in the Tertile1 group (with lower FVC% pred) were more likely to have a higher of body mass index (BMI), spinal deformities, and C-reactive protein (CRP) compared to the other two groups (P for trend < 0.001, 0.027, and 0.013, respectively). Among OSP patients, those in the Tertile1 group (with lower FEV1% pred) showed an increasing trend in cough symptoms and contralateral lung infection compared to the Tertile 2-3 group (P for trend 0.036 and 0.009, respectively). CONCLUSION: For TDL patients, we observed that Patients with high BMI, a higher proportion of spinal scoliosis, and abnormal elevation of CRP levels were more likely to have reduced FVC. Patients with decreased FEV1% pred have more frequent cough symptoms and a higher proportion of lung infections on the affected side.

The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.

The DNA-dependent protein kinase (DNA-PK), catalytic subunit, also known as DNA-PKcs, is complexed with the heterodimer Ku70/Ku80 to form DNA-PK holoenzyme, which is well recognized as initiator in the nonhomologous end joining (NHEJ) repair after double strand break (DSB). During NHEJ, DNA-PKcs is essential for both DNA end processing and end joining. Besides its classical function in DSB repair, DNA-PKcs also shows multifaceted functions in various biological activities such as class switch recombination (CSR) and variable (V) diversity (D) joining (J) recombination in B/T lymphocytes development, innate immunity through cGAS-STING pathway, transcription, alternative splicing, and so on, which are dependent on its function in NHEJ or not. Moreover, DNA-PKcs deficiency has been proven to be related with human diseases such as neurological pathogenesis, cancer, immunological disorder, and so on through different mechanisms. Therefore, it is imperative to summarize the latest findings about DNA-PKcs and diseases for better targeting DNA-PKcs, which have shown efficacy in cancer treatment in preclinical models. Here, we discuss the multifaceted roles of DNA-PKcs in human diseases, meanwhile, we discuss the progresses of DNA-PKcs inhibitors and their potential in clinical trials. The most updated review about DNA-PKcs will hopefully provide insights and ideas to understand DNA-PKcs associated diseases.

Dietary Supplementation of Compound Probiotics Improves Intestinal Health by Modulated Microbiota and Its SCFA Products as Alternatives to In-Feed Antibiotics.

Enterococcus faecium, Bifidobacterium, and Pediococcus acidilactici, as intestinal probiotics, have been proved to play a positive role in treating intestinal diseases, promoting growth and immune regulation in poultry. The aim of this study was to evaluate the effect of compound probiotics on growth performance, digestive enzyme activity, intestinal microbiome characteristics, as well as intestinal morphology in broiler chickens. Treatment diets with chlortetracycline and compound probiotics were used for two groups of sixty broilers each throughout the feeding process. Another group was fed the basal diet. The BW (2589.41 ± 13.10 g vs 2422.50 ± 19.08 g) and ADG (60.57 ± 0.31 g vs 56.60 ± 0.45 g) of the compound probiotics added feed treatment group were significantly increased, and the FCR was significantly decreased (P < 0.05). The supplementation of a compound probiotics enhanced the abundance of beneficial bacteria such as Lactobacillus, Faecalibacterium, and norank_f_norank_o_Clostridia_vadinBB60_group (P < 0.05), and modulated the cecal microbiota structure, thereby promoting the production of short-chain fatty acids (SCFAs) and elevating their levels (P < 0.05), particularly propionic and butyric acids. Furthermore, the administration of the compound probiotics supplements significantly enhanced the villi height, V/C ratio, and reduced the crypt depth (P < 0.05). In addition, the activity of digestive enzymes in the duodenum and jejunum was elevated (P < 0.05). Collectively, the selected compound probiotics supplemented in this experiment have demonstrated efficacy, warranting further application in practical production settings as a viable alternative to antibiotics, thereby facilitating efficient production and promoting gastrointestinal health.

HNRNPA2B1 stabilizes NFATC3 levels to potentiate its combined actions with FOSL1 to mediate vasculogenic mimicry in GBM cells.

BACKGROUND: Vasculogenic mimicry (VM) is an enigmatic physiological feature that influences blood supply within glioblastoma (GBM) tumors for their sustained growth. Previous studies identify NFATC3, FOSL1 and HNRNPA2B1 as significant mediators of VEGFR2, a key player in vasculogenesis, and their molecular relationships may be crucial for VM in GBM. AIMS: The aim of this study was to understand how NFATC3, FOSL1 and HNRNPA2B1 collectively influence VM in GBM. METHODS: We have investigated the underlying gene regulatory mechanisms for VM in GBM cell lines U251 and U373 in vitro and in vivo. In vitro cell-based assays were performed to explore the role of NFATC3, FOSL1 and HNRNPA2B1 in GBM cell proliferation, VM and migration, in the context of RNA interference (RNAi)-mediated knockdown alongside corresponding controls. Western blotting and qRT-PCR assays were used to examine VEGFR2 expression levels. CO-IP was employed to detect protein-protein interactions, ChIP was used to detect DNA-protein complexes, and RIP was used to detect RNA-protein complexes. Histochemical staining was used to detect VM tube formation in vivo. RESULTS: Focusing on NFATC3, FOSL1 and HNRNPA2B1, we found each was significantly upregulated in GBM and positively correlated with VM-like cellular behaviors in U251 and U373 cell lines. Knockdown of NFATC3, FOSL1 or HNRNPA2B1 each resulted in decreased levels of VEGFR2, a key growth factor gene that drives VM, as well as the inhibition of proliferation, cell migration and extracorporeal VM activity. Chromatin immunoprecipitation (ChIP) studies and luciferase reporter gene assays revealed that NFATC3 binds to the promoter region of VEGFR2 to enhance VEGFR2 gene expression. Notably, FOSL1 interacts with NFATC3 as a co-factor to potentiate the DNA-binding capacity of NFATC3, resulting in enhanced VM-like cellular behaviors. Also, level of NFATC3 protein in cells was enhanced through HNRNPA2B1 binding of NFATC3 mRNA. Furthermore, RNAi-mediated silencing of NFATC3, FOSL1 and HNRNPA2B1 in GBM cells reduced their capacity for tumor formation and VM-like behaviors in vivo. CONCLUSION: Taken together, our findings identify NFATC3 as an important mediator of GBM tumor growth through its molecular and epistatic interactions with HNRNPA2B1 and FOSL1 to influence VEGFR2 expression and VM-like cellular behaviors.

Association between dietary inflammatory index and NT-proBNP levels in US adults: A cross-sectional analysis.

BACKGROUND: With cardiovascular diseases standing as a leading cause of mortality worldwide, the interplay between diet-induced inflammation, as quantified by the Dietary Inflammatory Index (DII), and heart failure biomarker NT-proBNP has not been investigated in the general population. METHODS: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, encompassing 10,766 individuals. The relationship between the DII and NT-proBNP levels was evaluated through multivariable-adjusted regression models. To pinpoint crucial dietary components influencing NT-proBNP levels, the LASSO regression model was utilized. Stratified analyses were then conducted to examine the associations within specific subgroups to identify differential effects of the DII on NT-proBNP levels across diverse populations. RESULTS: In individuals without heart failure, a unit increase in the DII was significantly associated with an increase in NT-proBNP levels. Specifically, NT-proBNP levels rose by 9.69 pg/mL (95% CI: 6.47, 12.91; p < 0.001) without adjustments, 8.57 pg/mL (95% CI: 4.97, 12.17; p < 0.001) after adjusting for demographic factors, and 5.54 pg/mL (95% CI: 1.75, 9.32; p = 0.001) with further adjustments for health variables. In participants with a history of heart failure, those in the second and third DII quartile showed a trend towards higher NT-proBNP levels compared to those in the lowest quartile, with increases of 717.06 pg/mL (95% CI: 76.49-1357.63, p = 0.030) and 855.49 pg/mL (95% CI: 156.57-1554.41, p = 0.018). Significant interactions were observed in subgroup analyses by age (<50: ß = 3.63, p = 0.141; 50-75: ß = 18.4, p<0.001; >75: ß = 56.09, p<0.001), gender (men: ß = 17.82, p<0.001; women: ß = 7.43, p = 0.061),hypertension (ß = 25.73, p<0.001) and diabetes (ß = 38.94, p<0.001). CONCLUSION: This study identified a positive correlation between the DII and NT-proBNP levels, suggesting a robust link between pro-inflammatory diets and increased heart failure biomarkers, with implications for dietary modifications in cardiovascular risk management.