Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. Objectives: This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. Methods: The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1ß, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aß in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. Results: No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aß levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1ß, IL-6) compared to the VAN and VAS groups. Conclusion: Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aß protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Crosstalk between PML and p53 in response to TGF-ß1: A new mechanism of cardiac fibroblast activation.

Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.

Contrast-enhanced magnetic resonance angiography for monitoring an embolized renal artery aneurysm: A case report and literature review.

This case report describes a 69-year-old male patient with a renal artery aneurysm that was followed up with contrast-enhanced magnetic resonance angiography at 8 months after coil embolization treatment. Due to the disappearance of residual lumen with few metal artifacts, the therapeutic effect was satisfactory. At present, the indications for the treatment of renal artery aneurysms are still controversial and there are very few reports of postembolization images of renal artery aneurysms, with no criteria for reintervention and few reports for monitoring the embolized aneurysms. Further reports and research are still needed for the treatment of this rare disease.

Progress on spermatogonial stem cell microenvironment.

Spermatogonial stem cells (SSCs) are germ cells (GCs) with long-term self-renewal and differentiation potential in testis, namely tissue stem cells located on the basement membrane, whose self-renewal and differentiation are regulated by the surrounding microenvironment. In recent years, the research of SSCs has made a series of important progress, which brings the hope for the clinical treatment of some male infertility patients. Among them, the microenvironment is particularly important in regulating SSCs. The microenvironment is responsible for integrating the effects of different types of cell components, extracellular matrix, extracellular regulatory molecules and hormones on SSCs, thus regulating the fate of SSCs. The research on SSCs microenvironment has gradually become one of the main contents of stem cell research. In this review, we mainly summarize the cell composition, regulatory factors and characteristics of mouse SSCs microenvironment, thereby providing background information for in-depth study on the structure and function of SSCs microenvironment, and opportunity to find more abundant cell phenotypes and microenvironmental factors through multiple research models in the future.

[Biofilm Eradication Four-Step Strategy: Study of Using Self-Assembled Azithromycin/Rhamnolipid Nanoparticles for Removing Pseudomonas aeruginosa Biofilm].

OBJECTIVE: To investigate the in vitro eradicative effect of self-assembled azithromycin/rhamnolipid nanoparticles (AZI-RHL NPs) on P seudomonas aeruginosa ( P. aeruginosa) biofilm. METHODS: AZI-RHL NPs were prepared and characterized. The minimum inhibitory concentration (MIC) of AZI-RHL NPs on planktonic P. aeruginosa was measured by the broth microdilution method. The eradicative effect of AZI-RHL NPs on P. aeruginosa biofilm was evaluated via crystal violet staining and SYTO 9/PI live/dead staining. Fluorescence labeling was used to measure the eradicative effect of NPs on extracellular polymeric substances (EPS). In addition, crystal violet staining was performed to evaluate the inhibitory effect of AZI-RHL NPs on the adhesion of P. aeruginosa on human bronchial epithelial BEAS-2B cells. To investigate the ability of AZI-RHL NPs to penetrate mucus, the interaction between NPs and mucin was measured via particle size changes after co-incubation with mucin solution. RESULTS: The AZI-RHL NPs had a particle size of about 121 nm and were negatively charged on the surface, displaying a high encapsulation efficiency and a high drug loading capacity of 96.72% and 45.08% for AZI, respectively and 99.38% and 53.07% for RHL, respectively. The MIC of AZI-RHL NPs on planktonic P. aeruginosa was half of that of using AZI alone. AZI-RHL NPs displayed the capacity to effectively destroy the biofilm structure and remove the proteins and polysaccharides in EPS, eradicating biofilms in addition to reducing the survival rate of bacteria in the biofilm. AZI-RHL NPs were shown to have inhibited P. aeruginosa adhesion on BEAS-2B cells and prevented the residual bacteria from forming a new biofilm. There was no significant change in the particle size of NPs after co-incubation with mucin solution, indicating a weak interaction between NPs and mucin, and suggesting that NPs could penetrate the mucus and reach the P. aeruginosa infection sites. CONCLUSION: AZI-RHL NPs were able to effectively enhance the removal of P. aeruginosa biofilm through a four-step strategy of biofilm eradication, including penetrating the mucus, disintegrating the biofilm structure, killing the bacteria dispersed from biofilm, and preventing the adhesion of residual bacteria. We hope that this study will provide a replicable common strategy for the treatment of refractory infections caused by P. aeruginosa and other types of biofilms.

[Advances in the imaging studies of post-prostatectomy urinary incontinence].

Radical prostatectomy is a standard surgical strategy for prostate cancer though with a few postoperative complications such as urinary incontinence, erectile dysfunction and vesicle urethral anastomotic stricture. Post-prostatectomy incontinence, as a common complication seriously affecting the patient's quality of life, is mainly diagnosed according to the clinical symptoms and the results of urodynamic and imaging examinations. Patients with post-prostatectomy incontinence may undergo corresponding anatomic and functional changes, which can be clearly and directly observed in imaging examination. This review focuses on the advances in the imaging studies of post-prostatectomy urinary incontinence from the perspectives of MRI, ultrasound and cystourethrography.

Lrrc34 Is Highly Expressed in SSCs and Is Necessary for SSC Expansion In Vitro.

Objective To discover critical genes contributing to the stemness and maintenance of spermatogonial stem cells (SSCs) and provide new insights into the function of the leucine-rich repeat (LRR) family member Lrrc34 (leucine-rich repeat-containing 34) in SSCs from mice. Methods Bioinformatic methods, including differentially expressed gene (DEG), gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were used to uncover latent pluripotency-related genes. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence analyses were utilized to verify the mRNA and protein expression levels, respectively. RNA interference of Lrrc34 using siRNA was performed to detect its transient impact on SSCs. Results Eight DEGs between ID4-EGFP+ (G) and ID4-EGFP+/TSPAN8High (TH), eight DEGs between G and ID4-EGFP+/TSPAN8Low (TL) and eleven DEGs between TH and TL were discovered, and eleven protein-protein interaction (PPI) modules were found to be significant in the PPI network of DEGs. One of the DEGs, Lrrc34, was selected as a potential pluripotency-related gene due to its differential expression among ID4-EGFP+ spermatogonia subsets and its interaction with fibroblast growth factor 2 in the fifth module. Immunofluorescence experiments exhibited specific expression of Lrrc34 in a subpopulation of undifferentiated spermatogonia marked by LIN28A, and RT-PCR experiments confirmed the high expression of Lrrc34 in SSCs from P7 and adult mice. The transient knockdown of Lrrc34 in SSCs resulted in reduced colony sizes and significant changes in the transcriptome and apoptotic pathways. Conclusion Lrrc34 is highly expressed in mouse SSCs and is required for SSC proliferation in vitro through effects on transcriptome and signaling transduction pathways.

The complete mitochondrial genome of Glossaulax reiniana (Littorinimorpha: Naticidae).

In the present study, the complete mitochondrial genome of Glossaulax reiniana was determined using the next-generation sequencing. The circular genome was found to be 15,254 bp in length and had an overall nucleotide composition of 30.6% A, 14.1% C, 15.8% G, and 39.5% T. Similar to the typical caenogastropod mitochondrial genomes, it contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a potential control origin. All protein-coding genes started with standard initiation codons (ATA and ATG) and ended by TAA or TAG. The lengths of 12S ribosomal RNA and 16S ribosomal RNA were 948 and 1353 bp, respectively. The largest noncoding region considered to contain the origin of replication was 59 bp in length. The complete mitochondrial genome reported here would provide useful information for molecular phylogeny, genetic conservation, and sustainable management of G. reiniana.

[Cathode Electric Field Enhanced Removal of Nitrobenzene from Aqueous Solution Based on Activated Carbon Fibers (ACF)-Ozone Technique].

Through the environmental factors impact experiments,such as current intensity,initial pH value of the reaction solution,and the type and concentration of the electrolyte,effect and mechanism of electrochemically enhanced removal of nitrobenzene from aqueous solution on activated carbon fibers (ACF)-ozone technique were studied.The result showed that compared with the ACF-O3 system,the removal efficiency of NB in electrochemically enhanced ACF-O3 system was significantly improved.The effect of current intensity on the NB removal efficiency in the electrochemically enhanced ACF-O3 system was not significant.O3 concentration had some effect on the NB removal efficiency.The pH value of the initial reaction solution had a great influence on the catalytic activity of ACF in ACF-O3 system.The presence of inorganic salts such as sodium sulfate,sodium nitrate and sodium chloride inhibited the catalytic ability of ACF in O3 system.In addition,ACF was destroyed by ozone and the promoting effect of ACF was reduced.When the cathode electric field was applied on the surface of ACF,the removal effect of the organic compounds by ACF-O3 was improved significantly and the structure of ACF was not destroyed by ozone.

Early prediction of organ failure under the revised Atlanta classification.

BACKGROUND/AIMS: This study aimed to compare the ability of conventional laboratory markers and scoring systems to early predict organ failure (OF) and to differentiate between transient and persistent OF in patients with acute pancreatitis (AP) using the revised Atlanta classification. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 214 patients with AP between January 2014 and July 2015. The predictive values of laboratory markers were analyzed. The predictive accuracy of individual markers, extrapancreatic inflammation on computed tomography (EPIC), acute physiology and chronic health evaluation II (APACHE II), and bedside index for severity in acute pancreatitis (BISAP) scores were measured using the area under the receiver operating characteristic curve (AUROC). RESULTS: OF was diagnosed in 32 (15%) patients and persistent OF in 14 (6.5%). There were statistically significant differences between patients with and without OF with respect to white blood cell count, creatinine, blood urea nitrogen, lactate dehydrogenase, C-reactive protein, calcium (Ca), arterial partial pressure of oxygen (PaO2), base excess (BE), APACHE II, BISAP scores, and EPIC scores. Logistic regression analysis identified Ca, PaO2, and BE as independent predictors of OF. Using AUROC, the EPIC score had the highest accuracy for the early prediction of OF, which was 0.82. No significant differences were detected between patients with transient and persistent OF. CONCLUSION: Several laboratory markers and score systems were useful for the early prediction of OF in patients with AP, of which Ca, PaO2, and BE had highest predicting value, and EPIC score had the highest accuracy. We could not predict the duration of OF using laboratory markers.

[Study on phosphorus removal capability of constructed wetlands filled with broken bricks].

Physico-chemical properties of broken bricks (BB) were determined, as well as its phosphorus adsorption ability. The results showed that BB was appropriate for enrichment of microorganisms and growth of plants as filter medium in CWs, in addition, BB had high phosphorus adsorption ability. A vertical subsurface flow constructed wetland (VSSF) filled with BB was constructed in order to investigate the phosphorus removal effect of domestic sewage, and the phosphorus removal mechanism of VSSF was also explored. The results showed that the phosphorus removal rate of VSSF was more than 90%, which remained stable when the hydraulic loading rate was 5 cm x d(-1) and the running time was 1 a; adsorption and precipitation within BB played the greatest role in phosphorus removal; distribution characteristics of total phosphorus in the filter media were attributed to the vertical flow state of wastewater in the system, besides, the contents and chemical forms of elements which could precipitate with phosphorus should be principal factors for the phosphorus removal processes of BB. Therefore, BB might be an ideal filter medium used in CWs.

Screening of deoxyribozyme with high reversal efficiency against multidrug resistance in breast carcinoma cells.

Specific inhibition of P-glycoprotein (Pgp) expression, which is encoded by multidrug resistance gene-1 (MDR1), is considered a well-respected strategy to overcome multidrug resistance (MDR). Deoxyribozymes (DRz) are catalytic nucleic acids that could cleave a target RNA in sequence-specific manner. However, it is difficult to select an effective target site for DRz in living cells. In this study, target sites of DRz were screened according to MDR1 mRNA secondary structure by RNA structure analysis software. Twelve target sites on the surface of MDR1 mRNA were selected. Accordingly, 12 DRzs were synthesized and their suppression effect on the MDR phenotype in breast cancer cells was confirmed. The results showed that 4 (DRz 2, 3, 4, 9) of the 12 DRzs could, in a dose-dependent response, significantly suppress MDR1 mRNA expression and restore chemosensitivity in breast cancer cells with MDR phenotype. This was especially true of DRz 3, which targets the 141 site purine-pyrimidine dinucleotide. Compared with antisense oligonucleotide or anti-miR-27a inhibitor, DRz 3 was more efficient in suppressing MDR1 mRNA and Pgp protein expression or inhibiting Pgp function. The chemosensitivity assay also proved DRz 3 to be the best one to reverse the MDR phenotype. The present study suggests that screening targets of DRzs according to MDR1 mRNA secondary structure could be a useful method to obtain workable ones. We provide evidence that DRzs (DRz 2, 3, 4, 9) are highly efficient at reversing the MDR phenotype in breast carcinoma cells and restoring chemosensitivity.

2,2'-Ethyl-enediisoquinolinium dibromide dihydrate.

In the title compound, C(20)H(18)N(2) (2+)·2Br(-)·2H(2)O, the complete dication is generated by a crystallographic centre of symmetry. In the crystal, O-H⋯Br, C-H⋯Br and C-H⋯O hydrogen bonds and π-π stacking [shortest centroid-centroid separation = 3.657 (2) Å] help to establish the packing.

2-(2,4-Dichloro-phen-yl)acetic acid.

In the title compound, C(8)H(6)Cl(2)O(2), the dihedral angle between the C-C(=O)-OH carboxyl unit and the benzene ring is 70.70 (4)°. In the crystal, mol-ecules are linked into inversion dimers by pairs of O-H⋯O hydrogen bonds. The dimers are linked into chains extending along [001] by weak C-H⋯Cl inter-actions.

2-Methyl-3-p-tolyl-3H-benzo[e]indole-1-carbonitrile.

In the title compound, C(21)H(16)N(2), the dihedral angle between the benzoindole and tosyl ring systems is 71.99 (7)°. In the crystal, mol-ecules are linked into centrosymmetric dimers by pairs of C-H⋯N hydrogen bonds, generating R(2) (2)(16) loops.

2-mesitylacetic Acid.

In the title compound, C(11)H(14)O(2), the dihedral angle between the CCOO carboxyl unit and the benzene ring is 85.37 (7)°. In the crystal, the mol-ecules are linked into inversion dimers by pairs of O-H⋯O hydrogen bonds.

1-Meth-oxy-2-methyl-1H-benzo[f]indole-3-carbonitrile.

Apart from the methyl group of the meth-oxy fragment, the title compound, C(15)H(12)N(2)O, is almost planar (r.m.s. deviation = 0.045 Å); the C atom deviates from the mean plane by 1.216 (1) Å. In the crystal, π-π stacking [shortest centroid-centroid separation = 3.4652 (10) Å] and C-H⋯π inter-actions occur.