antiCD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury.

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people. Graphic abstract: Aged brains after TBI comprise two pools of CD8 + T cells . The aged brain has long been resided by a population of CD8 + T cells that's exhaustive and dysfunctional. Post TBI, due to BBB impairment, functional CD8 + T cells primarily migrate into the brain parenchyma. Aged, injury-associated microglia with upregulated MHC class I molecules can present neoantigens such as neuronal and/or myelin debris in the injured brains to functional CD8+ T, resulting in downstream CD8+ T cell cytotoxicity. aCD49d Ab treatment exerts its function by blocking the migration of functional effector CD8 + T cell population, leading to less cytotoxicity and resulting in improved TBI outcomes in aged mice.

Reactive Oxygen Species Responsive Multifunctional Fusion Extracellular Nanovesicles: Prospective Treatments for Acute Heart Transplant Rejection.

Heart transplantation offers life-saving treatment for patients with end-stage heart failure; however, ischemia-reperfusion injury (IRI) and subsequent immune responses remain significant challenges. Current therapies primarily target adaptive immunity, with limited options available for addressing IRI and innate immune activation. Although plant-derived vesicle-like nanoparticles show promise in managing diseases, their application in organ transplantation complications is unexplored. Here, this work develops a novel reactive oxygen species (ROS)-responsive multifunctional fusion extracellular nanovesicles carrying rapamycin (FNVs@RAPA) to address early IRI and Ly6C+Ly6G- inflammatory macrophage-mediated rejection in heart transplantation. The FNVs comprise Exocarpium Citri grandis-derived extracellular nanovesicles with anti-inflammatory and antioxidant properties, and mesenchymal stem cell membrane-derived nanovesicles expressing calreticulin with macrophage-targeting ability. A novel ROS-responsive bio-orthogonal chemistry approach facilitates the active targeting delivery of FNVs@RAPA to the heart graft site, effectively alleviating IRI and promoting the polarization of Ly6C+Ly6G- inflammatory macrophages toward an anti-inflammatory phenotype. Hence, FNVs@RAPA represents a promising therapeutic approach for mitigating early transplantation complications and immune rejection. The fusion-targeted delivery strategy offers superior heart graft site enrichment and macrophage-specific targeting, promising improved transplant outcomes.

Use of transrectal high-frequency ultrasound in assessment of middle compartment prolapse.

OBJECTIVE: To investigate the superiority of transrectal high-frequency ultrasound (TRUS) in precise assessment of middle compartment prolapse in comparison with routine transperineal ultrasound (TPUS). METHODS: Prospectively analyzed and compared detection rates of entire cervical length and uterine descent on TPUS and TRUS in 101 patients with pelvic organ prolapse (POP). RESULTS: Detection rates of entire cervix on TRUS were significantly higher than those on TPUS both at rest and during Valsalva maneuver (90.10% VS 49.50%, 92.08% VS 9.90% respectively, both p < 0.05). Uterine descent was able to be evaluated in 92.08% of patients by TRUS and in 5.94% of patients by TPUS, which was statistically significant (p < 0.05). The interobserver repeatability for the measurements of anterior lip, cervical canal and posterior lip on TRUS was excellent. The mean lengths of anterior lip, cervical canal and posterior lip were significantly increased during Valsalva maneuver than those measured at rest (p < 0.05). And mean length of anterior lip was longer than posterior lip both at rest and during Valsalva (p < 0.05). CONCLUSION: TRUS can significantly raise detection rates of entire cervix, and make the direct evaluation of uterine descent feasible. TRUS can be used as a complementary method to TPUS to attain more comprehensive and accurate presurgical imaging information in middle compartment prolapse patients.

Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Differential expression profiles and bioinformatics analysis of tRNA-derived small RNAs in epicardial fat of patients with atrial fibrillation.

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

The development strategies of amateur table tennis matches in China based on the SWOT-AHP model: a case study in Shanghai.

Given the significance of amateur sports matches in health promotion and city culture construction. It is essential to systematically analyze the organizational mode of city amateur matches and propose development strategies. This study aimed to investigate the sustainable development strategies for city amateur matches in China. This study adopted a hybrid model of combined SWOT and the AHP analysis, using the Shanghai City Amateur Table Tennis Matches (ATTM) as a case study. Results showed that 20 factors of the SWOT analysis were included, and the ranking of weights of the SWOT group are Strengths, Opportunities, Weaknesses and Threats, respectively, and the strategic vector (θ, ρ) are (74.21°, 0.5861). ATTM should adopt the S-O pioneering strategy and leverages its advantages and opportunities to promote further development. The findings indicate that ATTM with advanced organizational mode, has good internal strengths and external opportunities, which can enlighten the development of amateur table tennis matches for other regions and countries. Future research should apply the hybrid model to a broader range of events and conduct comparative analyses across countries and regions.

Interceed combined with bone marrow mesenchymal stem cells improves endometrial receptivity of intrauterine adhesion.

Background: This study aimed to investigate the impact of intrauterine adhesions (IUA) therapy and endometrial receptivity by implanting autologous bone marrow mesenchymal stem cells (BMSCs) into the Interceed and subsequently placing them in the uterine cavity of rats. Methods: Fifty rats were divided into 5 groups according to the random number table method (10 rats in each group). Following the development of the IUA model through mechanical injury, the animals were categorized into different treatment groups: the IUA model (intrauterine perfusion of saline), Interceed therapy (intrauterine placement of Interceed), BMSCs therapy (intrauterine perfusion of BMSCs), BMSCs + Interceed therapy (intrauterine placement of BMSCs + Interceed), and a control group (intrauterine perfusion of saline). The Hematoxylin-eosin (HE) staining technique was employed to identify and assess the pathological alterations in the endometrium. Additionally, it facilitated the quantification of endometrial glands and the determination of endometrial thickness. Masson staining was used to detect fibrosis in rat uterus. The number of microvascular density (MVD) was detected by immunohistochemistry (IHC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the levels of leukemia inhibitory factor (LIF), integrin ανß3, and vascular endothelial growth factor (VEGF) in uterine tissue. Male and female rats were combined in cages for reproductive and conception evaluation. Results: In comparison to the control, the number of endometrial glands in the IUA model was significantly reduced, and the degree of endometrial thinning and fibrosis was significantly increased (p < 0.05). Compared with the IUA model, the number of endometrial glands did not exhibit any significant alterations in endometrial thickness and MVD number. The expressions of LIF, integrin ανß3, and VEGF in the uterine tissue were not significantly improved with Interceed therapy, resulting in no significant improvement in the pregnancy rate (p > 0.05). The number of endometrial glands, endometrial thickness, and MVD in the BMSCs therapy group were significantly increased. Moreover, the expressions of LIF, integrin ανß3, and VEGF in uterine tissue exhibited a significant increase, leading to a comparatively higher pregnancy rate (p < 0.05). In the BMSCs + Interceed therapy group, the number of endometrial glands, endometrial thickness, and MVD were significantly increased, and the expressions of LIF, integrin ανß3, and VEGF in uterine tissue were significantly increased as well, along with a corresponding rise in the pregnancy rate (p < 0.05). Conclusion: The intrauterine placement of Interceed combined with BMSCs in IUA rats can thicken the damaged endometrium, increase the number of glands, promote endometrial angiogenesis, improve endometrial receptivity, and increase the rate of pregnancy in IUA rats.

Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis.

BACKGROUND: Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. AIM: To explore the effect of taurine on aHSC proliferation and the mechanisms involved. METHODS: Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. RESULTS: Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. CONCLUSION: Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.

Bioactive poly(salicylic acid)-poly(citric acid) scaffolds improve diabetic wound repair via regulating HIF-1α, Nrf2 and macrophage.

Diabetic wounds environment is over-oxidized, over-inflammatory, leading to difficulties in regenerating blood vessels, and retardation of healing in diabetic wounds. Therefore, diabetic wounds can be treated from the perspective of scavenging oxidative free radicals and reducing the level of inflammation. Herein, we report a bioactive poly(salicylic acid)-poly(citric acid) (FPSa-PCG) hydrogel for diabetic wound repair. The FPSa-PCG hydrogel shows abilities of antioxidation, anti-inflammation, and regulation of macrophage phenotype. The FPSa-PCG hydrogel showed good biocompatibility, and obtain the abilities of promotion of macrophages migration, reduction of ROS generation, suppression of the M1-type macrophage polarization. FPSa and PCG could synergistically enhance the angiogenesis through upregulating the mRNA expression of HIF1Α, VEGF, and CD31 in endothelial cells and reduce the ROS level of macrophages through upregulating the mRNA expression of Nrf2. The in vivo diabetic wound model confirmed the promoting effect of FPSa-PCG hydrogel on wound closure in diabetes. The further studies found that FPSa-PCG hydrogel could induce the CD31 protein expression in the subcutaneous tissue and inhibit the TNF-a protein expression. This work shows that the simple composition FPSa-PCG hydrogel has a promising therapeutic potential in the treatment of diabetic wounds.

Long-read sequencing unveils novel somatic variants and methylation patterns in the genetic information system of early lung cancer.

Lung cancer poses a global health challenge, necessitating advanced diagnostics for improved outcomes. Intensive efforts are ongoing to pinpoint early detection biomarkers, such as genomic variations and DNA methylation, to elevate diagnostic precision. We conducted long-read sequencing on cancerous and adjacent non-cancerous tissues from a patient with lung adenocarcinoma. We identified somatic structural variations (SVs) specific to lung cancer by integrating data from various SV calling methods and differentially methylated regions (DMRs) that were distinct between these two tissue samples, revealing a unique methylation pattern associated with lung cancer. This study discovered over 40,000 somatic SVs and over 180,000 DMRs linked to lung cancer. We identified approximately 700 genes of significant relevance through comprehensive analysis, including genes intricately associated with many lung cancers, such as NOTCH1, SMOC2, CSMD2, and others. Furthermore, we observed that somatic SVs and DMRs were substantially enriched in several pathways, such as axon guidance signaling pathways, which suggests a comprehensive multi-omics impact on lung cancer progression across various biological investigation levels. These datasets can potentially serve as biomarkers for early lung cancer detection and may hold significant value in clinical diagnosis and treatment applications.

"Four-In-One" Multifunctional Dandelion-Like Gold@platinum Nanoparticles-Driven Multimodal Lateral Flow Immunoassay.

The traditional lateral flow immunoassay (LFIA) with a single signal output mode may encounter challenges such as low sensitivity, poor detection range, and susceptibility to external interferences. These limitations hinder its ability to meet the growing demand for advanced LFIA. To address these issues, the rational development of multifunctional labels for multimodal LFIA emerges as a promising strategy. Herein, this study reports a multimodal LFIA using "four-in-one" multifunctional dandelion-like gold@platinum nanoparticles (MDGP). The inherent properties of MDGP, such as the broad absorption spectrum, porous dandelion-like nanostructure, and bimetallic composition with gold and platinum, endow them with capacities in dual spectral-overlapped fluorescence quenching, optical readout, catalytic activity, and photothermal effect. Benefiting from their multifunctional properties, the MDGP-LFIA enables multimodal outputs including fluorescent, colorimetric, and photothermal signals. This multimodal MDGP-LFIA allows for the detection of acetamiprid at a range of 0.01-50 ng mL-1, with the lowest qualitative and quantitative detection results of 0.5 and 0.008 ng mL-1, respectively, significantly better than the traditional gold nanoparticles-based LFIA. The diversity, complementarity, and synergistic effect of integrated output signals in this multimodal MDGP-LFIA improve the flexibility, practicability, and accuracy of detection, holding great promise as a point-of-care testing platform in versatile application scenarios.

NEAT1 repression by MED12 creates chemosensitivity in p53 wild-type breast cancer cells.

Breast cancer is often treated with chemotherapy. However, the development of chemoresistance results in treatment failure. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to contribute to chemoresistance in breast cancer cells. In studying the transcriptional regulation of NEAT1 using multi-omics approaches, we showed that NEAT1 is up-regulated by 5-fluorouracil in breast cancer cells with wild-type cellular tumor antigen p53 but not in mutant-p53-expressing breast cancer cells. The regulation of NEAT1 involves mediator complex subunit 12 (MED12)-mediated repression of histone acetylation marks at the promoter region of NEAT1. Knockdown of MED12 but not coactivator-associated arginine methyltransferase 1 (CARM1) induced histone acetylation at the NEAT1 promoter, leading to elevated NEAT1 mRNAs, resulting in a chemoresistant phenotype. The MED12-dependent regulation of NEAT1 differs between wild-type and mutant p53-expressing cells. MED12 depletion led to increased expression of NEAT1 in a wild-type p53 cell line, but decreased expression in a mutant p53 cell line. Chemoresistance caused by MED12 depletion can be partially rescued by NEAT1 knockdown in p53 wild-type cells. Collectively, our study reveals a novel mechanism of chemoresistance dependent on MED12 transcriptional regulation of NEAT1 in p53 wild-type breast cancer cells.

Mammographically detected breast clustered microcalcifications localized by chest thin-section computed tomography.

BACKGROUND: To explore the capability and clinical significance of chest thin-section computed tomography (CT) for localization of mammographically detected clustered microcalcifications. METHODS: A total of 69 patients with 71 mammographically detected clustered microcalcifications received surgical biopsy under the guidance of mammography (MG), CT was used to localize calcifications combined with MG if calcifications can be seen on CT. Intraoperative mammography of the specimens were performed in all cases for identification of the resected microcalcifications. The clinical, imaging and pathological information of these patients were analyzed. RESULTS: A total of 42 (59.15%) cases of calcifications were localized by CT + MG, 29 (40.85%) cases were guided only by the mammography. All suspicious calcifications on the mammography were successfully removed. Pathological results showed 42 cases were cancer, 23 cases were benign, and 6 cases were atypical hyperplasia. The mean age in the CT + MG group was older than that of the MG group (54.12 vs. 49.27 years; P = 0.014). The maximum diameter of clusters of microcalcifications on mammography in the CT + MG group was larger than that of the MG group [(cranio-caudal view, 1.52 vs. 0.61 mm, P = 0.000; mediolateral oblique (MLO) view, 1.53 vs. 0.62 mm, P = 0.000)]. The gray value ratio (calcified area / paraglandular; MLO, P = 0.004) and the gray value difference (calcified area - paraglandular; MLO, P = 0.005) in the CT + MG group was higher than that of the MG group. Multivariate analysis showed that the max diameter of clusters of microcalcifications (MLO view) was a significant predictive factor of localization by CT in total patients (P = 0.001). CONCLUSIONS: About half of the mammographically detected clustered microcalcifications could be localized by thin-section CT. Maximum diameter of clusters of microcalcifications (MLO view) was a predictor of visibility of calcifications by CT. Chest thin-section CT may be useful for localization of calcifications in some patients, especially for calcifications that are only visible in one view on the mammography.

Identification of Shared Biomarkers and Immune Infiltration Signatures between Vitiligo and Hashimoto's Thyroiditis.

Background: Vitiligo and Hashimoto's thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers. Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR). Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity. Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.

Effects of traditional Chinese exercises in fibromyalgia syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVES: To explore the efficacy and safety of five traditional Chinese exercises (TCEs) in patients with fibromyalgia syndrome (FMS). METHODS: The PubMed, Embase, Scopus, ProQuest, Web of Science, Cochrane, CNKI, WanFang, and VIP databases were comprehensively searched for randomized controlled trials (RCTs) related to TCEs published from inception until February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were used to determine the combined effects of the intervention, and the Cochrane risk-of-bias assessment tool and Review 5.2 software were used to assess methodological quality. The data were extracted and analyzed by the Stata15.0 random effects model. RESULTS: Nineteen RCTs including 1315 participants were included in the analysis. The studies were found to be heterogeneous (I2 =86.2, P = 0.000), and thus a random effects model was used to combine the data. The results showed that traditional Chinese exercises had potentially beneficial effects on reducing pain (SMD =-0.66,95% CI [-1.08, -0.25], P = 0.002), improving sleep (SMD = -0.35,95% CI [-0.68,0. 01], P = 0.041) and relieving depression (SMD= -0.24,95% CI [-0.47, -0.02], P = 0.034) in FMS patients. However, no significant effects were found on improved quality of life (SMD =-0.20,95% CI [-0.48,0.09], P = 0.176). CONCLUSIONS: TCEs can improve pain, sleep quality and depression in patients with FMS and are safe. However, they do not improve the quality of life significantly. Further large-scale, high-quality, and multi-center RCTs are required to verify the efficacy of TCEs.

Sweet taste receptors play roles in artificial sweetener-induced enhanced urine output in mice.

Sweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear. In this study, we investigated the relationship between urinary excretion and the sweet taste receptor expression in mice after three artificial sweeteners exposure in a higher or lower concentration via animal behavioral studies, western blotting, and real-time quantitative PCR experiment in rodent model. Our results showed that high dose of acesulfame potassium and saccharin can significantly enhance the urine output and there was a positive correlation between K+ and urination volume. The acesulfame potassium administration assay of T1R3 knockout mice showed that artificial sweeteners may affect the urine output directly through the sweet taste signaling pathway. The expression of T1R3 encoding gene can be up-regulated specifically in bladder but not in kidney or other organs we tested. Through our study, the sweet taste receptors, distributing in many tissues as bladder, were indicated to function in the enhanced urine output. Different effects of long-term exposure to the three artificial sweeteners were shown and acesulfame potassium increased urine output even at a very low concentration.

The synbiotic combination of probiotics and inulin improves NAFLD though modulating gut microbiota.

Prebiotics can promote the growth of probiotics, cocombine of these is called synbiotics, and synbiotics is powerful regulators of gut microbiota. Intestinal microbiota plays an important role in nonalcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. This study aims to investigate the effect of synbiotics combination of probiotics (Streptococcus Bifidobacterium and Streptococcus thermophilus) and prebiotics (Inulin) in vivo model of early NAFLD using yogurt as carrier. The results demonstrate that the yogurt with synbiotics combination group (HS) improves the biochemical indicators related to total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and insulin resistance (IR) in mice (P< .01). HS improves the development of lipid metabolism and inflammation by activating the AMPK and NFκB signaling pathway. In addition, HS restores the intestinal barrier dysfunction and inflammation caused by a high-fat diet. The 16S rRNA demonstrates that the gut microbiota composition of mice treated with HS is significantly altered specifically, the Firmicutes/Bacteroidetes ratio is significantly lower than in HFD-fed mice (P< .01). Our findings suggest the applicability of HS in preventing obesity-related NAFLD via its antioxidant, anti-inflammatory, and improved lipid metabolism by the gut-liver axis and provide a solid theoretical foundation for developing prebiotics for the prevention of NAFLD.

Oxidative potential, environmentally persistent free radicals and reactive oxygen species of size-resolved ambient particles near highways.

Particulate matter (PM) is a group of atmospheric pollutants with an uncertain toxicity, particularly when collected near highways. This study examined the oxidative potential (OP) of, as well as the environmentally persistent free radicals (EPFRs) and reactive oxygen species (ROS) present in PM samples collected near highways in Xiamen, China. Our findings revealed that PM had a relatively high OP, ranging from 3.8 to 18.5 nmol/min/µg, surpassing values reported in previous research. The oxidative potential of the water-insoluble fraction (OPWIS), which accounted for 68% of the total oxidative potential (OPTotal), demonstrated rapid toxicity, whereas the oxidative potential of the water-soluble fraction (OPWS) displayed a steadier toxicity release pattern. The primary free radicals detected in PM were oxygen-centered. The measured concentration of EPFRs was 6.073 × 1014 spins/m3, which is lower than that reported in previous studies, possibly because of the high relative humidity of the road environment in Xiamen. We also investigated the interaction between PM and water near highways and observed the generation of R and OH radicals. Additionally, we analysed the sample composition and evaluated the contributions of the different components to OPTotal. Transition metals (Fe, Cu, and Zn) were identified as the major contributors, accounting for 33.2% of the OPTotal. The positive correlation observed between EPFRs and ROS suggests that EPFRs may be involved in ROS generation. The correlation analysis indicated that the oxidative potential measured using the DTT method (OPDTT) could serve as an indicator of ROS generation. Finally, based on the relationship between OPDTT, EPFRs, and ROS, we propose that reducing the emission of transition metals, particularly Fe, represents an effective control measure for mitigating PM toxicity near highways.

Engineering Single-Component Antibacterial Anti-inflammatory Polyitaconate-Based Hydrogel for Promoting Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing and Skin Regeneration.

Hydrogel wound dressings play a crucial role in promoting the healing of drug-resistant bacterially infected wounds. However, their clinical application often faces challenges such as the use of numerous components, a complicated preparation process, and insufficient biological activity. Itaconic acid, known for its excellent biological and reaction activities, has not been extensively studied for the preparation of itaconic acid-based hydrogels and their application in infected wound healing. Therefore, there is a need to develop a multifunctional single-component itaconic acid-based hydrogel that is easy to synthesize and holds promising prospects for clinical use in promoting the healing of infected wounds. In this study, we present a single-component polyitaconate-based hydrogel (PICGI) with antibacterial, anti-inflammatory, and biological activity. The PICGI hydrogel demonstrates great potential in promoting healing of infected wounds and skin regeneration. It exhibits desirable thermosensitive, injectable, and adhesive properties, as well as broad-spectrum antibacterial activity and anti-inflammatory effects. Furthermore, the PICGI hydrogel is biocompatible and significantly enhances the migration and tube formation of endothelial cells. In the case of drug-resistant bacterially infected wounds, the PICGI hydrogel effectively inhibits bacterial infection and inflammation, promotes angiogenesis, and facilitates collagen deposition, thereby accelerating the healing and regeneration of the skin. This study highlights the promising application of the PICGI hydrogel as a single-component hydrogel in tissue repair associated with bacterial infection and inflammation. Moreover, the simplicity of its components, convenient preparation process, and sufficient biological activity make the PICGI hydrogel highly suitable for promotion and clinical application.

Effect of resistance training programs differing in set structure on muscular hypertrophy and performance in untrained young men.

Purpose: This study aimed to compare the effects on muscle hypertrophy and muscular performance of two resistance training (RT) programs that differed only in set structure: traditional set structure (TS) vs. rest redistribution set structure (RR). Methods: Thirty untrained young men were pair-matched and randomly assigned to a TS (n = 15) or an RR (n = 15) protocol based on individual baseline measures. Participants trained for 8 weeks using the same total body RT routines performed twice weekly. The TS protocol comprised four sets of 10 repetitions per exercise with 120-s interset rest, and the RR involved eight sets of five repetitions per exercise with 51-s interset rest. Participants were tested pre- and post-intervention for body composition, regional muscle thickness, upper- and lower-body muscle maximal strength [1-repetition maximum (1RM)], mean power output and velocity at 75% 1RM and muscular endurance (repetitions to failure at 70% 1RM). Results: Compared to baseline, both groups exhibited equally significantly decreased body fat mass (p < 0.05), increased fat-free mass (p < 0.001), muscle thickness (p < 0.05), upper and lower-body muscular maximal strength (p < 0.001) and endurance performance (p < 0.001). However, both groups only increase the lower-body power output (p < 0.001) but not the upper-body (p > 0.05). No significant differences existed between groups for all measurements (p > 0.05). Conclusion: These results suggest that RR and TS groups have similar effects for improving muscle hypertrophy and performance in untrained young men.