Smoking Cessation With 20 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) Applied to Two Brain Regions: A Pilot Study

Chronic smoking impairs brain functions in the prefrontal cortex and the projecting meso-cortical limbic system. The purpose of this pilot study is to examine whether modulating the frontal brain activity using high-frequency repetitive transcranial magnetic stimulation (rTMS) can improve smoking cessation and to explore the changing pattern of the brain activity after treatment. Fourteen treatment-seeking smokers were offered a program involving 10 days of rTMS treatment with a follow-up for another 25 days. A frequency of 20 Hz rTMS was sequentially applied on the left dorso-lateral prefrontal cortex (DLPFC) and the superior medial frontal cortex (SMFC). The carbon monoxide (CO) level, withdrawal, craving scales, and neuroimaging data were collected. Ten smokers completed the entire treatment program, and 90% of them did not smoke during the 25-day follow-up time. A significant smoking craving reduction and resting brain activity reduction measured by the cerebral blood flow (CBF) and brain entropy (BEN) were observed after 10 days of 20 Hz rTMS treatments compared to the baseline. Although limited by sample size, these pilot findings definitely showed a high potential of multiple-target high-frequency rTMS in smoking cessation and the utility of fMRI for objectively assessing the treatment effects

miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging

Variations in bacterial diversity and community structure in the sediments of an alkaline lake in Inner Mongolia plateau, China

Alkaline lakes are a special aquatic ecosystem that act as important water and alkali resource in the arid-semiarid regions. The primary aim of the study is to explore how environmental factors affect community diversity and structure, and to find whether there are key microbes that can indicate changes in environmental factors in alkaline lakes. Therefore, four sediment samples (S1, S2, S3, and S4) were collected from Hamatai Lake which is an important alkali resource in Ordos’ desert plateau of Inner Mongolia. Samples were collected along the salinity and alkalinity gradients and bacterial community compositions were investigated by Illumina Miseq sequencing. The results revealed that the diversity and richness of bacterial community decreased with increasing alkalinity (pH) and salinity, and bacterial community structure was obviously different for the relatively light alkaline and hyposaline samples (LAHO; pH 8.5; salinity > 20‰). Firmicutes, Proteobacteria and Bacteriodetes were observed to be the dominant phyla. Furthermore, Acidobacteria, Actinobacteria, and low salt-tolerant alkaliphilic nitrifying taxa were mainly distributed in S1 with LAHO characteristic. Firmicutes, Clostridia, Gammaproteobacteria, salt-tolerant alkaliphilic denitrifying taxa, haloalkaliphilic sulfur cycling taxa were mainly distributed in S2, S3 and S4, and were well adapted to haloalkaline conditions. Correlation analysis revealed that the community diversity (operational taxonomic unit numbers and/or Shannon index) and richness (Chao1) were significantly positively correlated with ammonium nitrogen (r = 0.654, p < 0.05; r = 0.680, p < 0.05) and negatively correlated with pH (r = −0.924, p < 0.01; r = −0.800, p < 0.01; r = −0.933, p < 0.01) and salinity (r = −0.615, p < 0.05; r = −0.647, p < 0.05). A redundancy analysis and variation partitioning analysis revealed that pH (explanation degrees of 53.5%, pseudo-F = 11.5, p < 0.01), TOC/TN (24.8%, pseudo-F = 10.3, p < 0.05) and salinity (9.2%, pseudo-F = 9.5, p < 0.05) were the most significant factors that caused the variations in bacterial community structure. The results suggested that alkalinity, nutrient salt and salinity jointly affect bacterial diversity and community structure, in which one taxon (Acidobacteria), six taxa (Cyanobacteria, Nitrosomonadaceae, Nitrospira, Bacillus, Lactococcus and Halomonas) and five taxa (Desulfonatronobacter, Dethiobacter, Desulfurivibrio, Thioalkalivibrio and Halorhodospira) are related to carbon, nitrogen and sulfur cycles, respectively. Classes Clostridia and Gammaproteobacteria might indicate changes of saline-alkali conditions in the sediments of alkaline lakes in desert plateau