Zigzag magnetic order in a novel tellurate compound Na4−δ_{4-\delta}NiTeO6_{6} with S\mathit{S} = 1 chains

Na$_{4-\delta}$NiTeO$_{6}$ is a rare example in the transition-metal tellurate family of realizing an $S$ = 1 spin-chain structure. By performing neutron powder diffraction measurements, the ground-state magnetic structure of Na$_{4-\delta}$NiTeO$_{6}$ is determined. These measurements reveal that below $T\rm_{N}$ ${\sim}$ 6.8(2) K, the Ni$^{2+}$ moments form a screwed ferromagnetic (FM) spin-chain structure running along the crystallographic $a$ axis but these FM spin chains are coupled antiferromagnetically along the $b$ and $c$ directions, giving rise to a magnetic propagation vector of $k$ = (0, 1/2, 1/2). This zigzag magnetic order is well supported by first-principles calculations. The moment size of Ni$^{2+}$ spins is determined to be 2.1(1) $\mu$$\rm_{B}$ at 3 K, suggesting a significant quenching of the orbital moment due to the crystalline electric field (CEF) effect. The previously reported metamagnetic transition near $H\rm_{C}$ ${\sim}$ 0.1 T can be understood as a field-induced spin-flip transition. The relatively easy tunability of the dimensionality of its magnetism by external parameters makes Na$_{4-\delta}$NiTeO$_{6}$ a promising candidate for further exploring various types of novel spin-chain physics.Comment: 10 pages, 6 figure

The dual role of glioma exosomal microRNAs: glioma eliminates tumor suppressor miR-1298-5p via exosomes to promote immunosuppressive effects of MDSCs

Clear evidence shows that tumors could secrete microRNAs (miRNAs) via exosomes to modulate the tumor microenvironment (TME). However, the mechanisms sorting specific miRNAs into exosomes are still unclear. In order to study the biological function and characterization of exosomal miRNAs, we performed whole-transcriptome sequencing in 59 patients’ whole-course cerebrospinal fluid (CSF) small extracellular vesicles (sEV) and matched glioma tissue samples. The results demonstrate that miRNAs could be divided into exosome-enriched miRNAs (ExomiRNAs) and intracellular-retained miRNAs (CLmiRNAs), and exosome-enriched miRNAs generally play a dual role. Among them, miR-1298-5p was enriched in CSF exosomes and suppressed glioma progression in vitro and vivo experiments. Interestingly, exosomal miR-1298-5p could promote the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) to facilitate glioma. Therefore, we found miR-1298-5p had different effects on glioma cells and MDSCs. Mechanically, downstream signaling pathway analyses showed that miR-1298-5p plays distinct roles in glioma cells and MDSCs via targeting SETD7 and MSH2, respectively. Moreover, reverse verification was performed on the intracellular-retained miRNA miR-9-5p. Thus, we confirmed that tumor-suppressive miRNAs in glioma cells could be eliminated through exosomes and target tumor-associated immune cells to induce tumor-promoting phenotypes. Glioma could get double benefit from it. These findings uncover the mechanisms that glioma selectively sorts miRNAs into exosomes and modulates tumor immunity.publishedVersio

SPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner

As one of the most common post-transcriptional modifications of mRNAs and noncoding RNAs, N6-methyladenosine (m6A) modification regulates almost every aspect of RNA metabolism. Evidence indicates that dysregulation of m6A modification and associated proteins contributes to glioblastoma (GBM) progression. However, the function of fat mass and obesity-associated protein (FTO), an m6A demethylase, has not been systematically and comprehensively explored in GBM. Here, we found that decreased FTO expression in clinical specimens correlated with higher glioma grades and poorer clinical outcomes. Functionally, FTO inhibited growth and invasion in GBM cells in vitro and in vivo. Mechanistically, FTO regulated the m6A modification of primary microRNA-10a (pri-miR-10a), which could be recognized by reader HNRNPA2B1, recruiting the microRNA microprocessor complex protein DGCR8 and mediating pri-miR-10a processing. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor SPI1, which could be specifically disrupted by the SPI1 inhibitor DB2313. Treatment with this inhibitor restored endogenous FTO expression and decreased GBM tumor burden, suggesting that FTO may serve as a novel prognostic indicator and therapeutic molecular target of GBM.publishedVersio

Creatine Acts as a Mediator of the Causal Effect of Obesity on Puberty Onset in Girls: Evidence from Mediation Mendelian Randomization Study

Epidemiological studies have linked obesity to the onset of puberty, while its causality and the potential metabolite mediators remain unclear. We employed a two-sample Mendelian randomization (MR) design to evaluate the causal effects of obesity on puberty onset and its associated diseases including type 2 diabetes (T2D) and cardiovascular diseases (CVDs). The potential mediators in this pathway were further explored using a two-step MR design. The robustness of our findings was evaluated using sensitivity analyses. Our MR results revealed that childhood obesity/BMI were causally associated with an increased Tanner stage in girls, younger age at menarche, and increased risk of adulthood T2D and CVD. However, neither childhood BMI nor obesity had a causal effect on the Tanner stage in boys. Mediation analysis further indicated that increased creatine served as a mediator for the causal pathway from childhood obesity/BMI to the Tanner stage of girls, while early puberty onset in girls played a mediating role in the pathway linking childhood obesity to increased risk of adulthood T2D and CVD. This study indicated that the risk of early puberty onset in girls and its associated health issues can be potentially reduced by preventing childhood obesity. The involvement of creatine in this process needs to be further validated and explored

Bidirectional Mediation Effects between Intratumoral Microbiome and Host DNA Methylation Changes Contribute to Stomach Adenocarcinoma

ABSTRACT The induction of aberrant DNA methylation is the major pathway by which Helicobacter pylori infection induces stomach adenocarcinoma (STAD). The involvement of the non-H. pylori gastric microbiota in this mechanism remains to be examined. RNA sequencing data, clinical information, and DNA methylation data were obtained from The Cancer Genome Atlas (TCGA) STAD project. The Kraken 2 pipeline was employed to explore the microbiome profiles. The microbiome was associated with occurrence, distal metastasis, and prognosis, and differential methylation changes related to distal metastasis and prognosis were analyzed. Bi-directional mediation effects of the intratumoral microbiome and host DNA methylation changes on the metastasis and prognosis of STAD were identified by mediation analysis. The expression of the ZNF215 gene was verified by real-time quantitative PCR (RT-qPCR). A cell counting kit 8 (CCK8) cell proliferation experiment and a cell clone formation experiment were used to evaluate the proliferation and invasion abilities of gastric cells. Our analysis revealed that H. pylori and other cancer-related microorganisms were related to the occurrence, progression, or prognosis of STAD. The related methylated genes were particularly enriched in related cancer pathways. Kytococcus sedentarius and Actinomyces oris, which interacted strongly with methylation changes in immune genes, were associated with prognosis. Cell experiments verified that Staphylococcus saccharolyticus could promote the proliferation and cloning of gastric cells by regulating the gene expression level of the ZNF215 gene. Our study suggested that the bi-directional mediation effect between intratumoral microorganisms and host epigenetics was key to the distal metastasis of cancer cells and survival deterioration in the tumor microenvironment of stomach tissues of patients with STAD. IMPORTANCE The burgeoning field of oncobiome research declared that members of the intratumoral microbiome besides Helicobacter pylori existed in tumor tissues and participated in the occurrence and development of gastric cancer, and the methylation of host DNA may be a potential target of microbes and their metabolites. Current research focuses mostly on species composition, but the functional genes of the members of the microbiota are also key to their interaction with the host. Therefore, we focused on characterizing the species composition and functional gene composition of microbes in gastric cancer, and we suggest that microbes may further participate in the occurrence and development of cancer by influencing abnormal epigenetic changes in the host. Some key bioinformatics analysis results were verified by in vitro experiments. Thus, we consider that the tumor microbiota-host epigenetic axis of gastric cancer microorganisms and the host explains the mechanism of the microbiota participating in cancer occurrence and development, and we make some verifiable experimental predictions

DataSheet_1_Identifying and ranking causal microbial biomarkers for colorectal cancer at different cancer subsites and stages: a Mendelian randomization study.docx

IntroductionThe gut microbiome is directly involved in colorectal carcinogenesis, but much of the epidemiological evidence for the effect of the gut microbiome on colorectal cancer (CRC) risk comes from observational studies, and it is unclear whether identified microbial alterations are the cause or consequence of CRC development.MethodsUnivariate Mendelian randomization (MR) analysis and multivariate MR analysis based on Bayesian model averaging were performed to comprehensively explore the microbial risk factors associated with CRC. The Network Module Structure Shift method was used to identify microbial biomarkers associated with CRC. Mediation analysis was used to explore the dietary habits-microbiota-CRC pathway.ResultsThe results of the four methods showed that 9 bacteria had a robust causal relationship with the development of CRC. Among them, Streptococcus thermophilus reduced the risk of CRC; Eubacterium ventriosum and Streptococcus were beneficial bacteria of malignant tumors of colon (CC); Erysipelotrichaceae was a protective factor for malignant tumors of rectal (CR); Bacteroides ovatus was a risk factor for benign tumors. Finally, the mediation analysis revealed 10 pathways by which dietary regulation bacteria affected the risk of CRC, including alcohol consumption increased the risk of CC by reducing the abundance of Eubacterium ventriosum (mediated proportion: 43.044%), and the mediated proportion of other pathways was 7.026%-34.22%.DiscussionThese findings will contribute to the understanding of the different carcinogenic mechanisms of intestinal flora in the colon and rectum and the risk of tumor transformation, thereby aiding CRC prevention, early screening, and the development of future strategies to reduce CRC risk.</p

Causal Effects of Gut Microbiota on Sleep-Related Phenotypes: A Two-Sample Mendelian Randomization Study

Increasing evidence suggests a correlation between changes in the composition of gut microbiota and sleep-related phenotypes. However, it remains uncertain whether these associations indicate a causal relationship. The genome-wide association study summary statistics data of gut microbiota (n = 18,340) was downloaded from the MiBioGen consortium and the data of sleep-related phenotypes were derived from the UK Biobank, the Medical Research Council-Integrative Epidemiology Unit, Jones SE, the FinnGen consortium. To test and estimate the causal effect of gut microbiota on sleep traits, a two-sample Mendelian randomization (MR) approach using multiple methods was conducted. A series of sensitive analyses, such as horizontal pleiotropy analysis, heterogeneity test, MR Steiger directionality test and “leave-one-out” analysis as well as reverse MR analysis, were conducted to assess the robustness of MR results. The genus Anaerofilum has a negative causal effect on getting up in the morning (odd ratio = 0.977, 95% confidence interval: 0.965–0.988, p = 7.28 × 10−5). A higher abundance of order Enterobacteriales and family Enterobacteriaceae contributed to becoming an “evening person”. Six and two taxa were causally associated with longer and shorter sleep duration, respectively. Specifically, two SCFA-produced genera including Lachnospiraceae UCG004 (odd ratio = 1.029, 95% confidence interval = 1.012–1.046, p = 6.11 × 10−4) and Odoribacter contribute to extending sleep duration. Two obesity-related genera such as Ruminococcus torques (odd ratio = 1.024, 95% confidence interval: 1.011–1.036, p = 1.74 × 10−4) and Senegalimassilia were found to be increased and decreased risk of snoring, respectively. In addition, we found two risk taxa of insomnia such as the order Selenomonadales and one of its classes called Negativicutes. All of the sensitive analysis and reverse MR analysis results indicated that our MR results were robust. Our study revealed the causal effect of gut microbiota on sleep and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia, which has the potential to provide new perspectives for future mechanistic and clinical investigations of microbiota-mediated sleep abnormal patterns and provide clues for developing potential microbiota-based intervention strategies for sleep-related conditions

DataSheet_2_Identifying and ranking causal microbial biomarkers for colorectal cancer at different cancer subsites and stages: a Mendelian randomization study.docx

IntroductionThe gut microbiome is directly involved in colorectal carcinogenesis, but much of the epidemiological evidence for the effect of the gut microbiome on colorectal cancer (CRC) risk comes from observational studies, and it is unclear whether identified microbial alterations are the cause or consequence of CRC development.MethodsUnivariate Mendelian randomization (MR) analysis and multivariate MR analysis based on Bayesian model averaging were performed to comprehensively explore the microbial risk factors associated with CRC. The Network Module Structure Shift method was used to identify microbial biomarkers associated with CRC. Mediation analysis was used to explore the dietary habits-microbiota-CRC pathway.ResultsThe results of the four methods showed that 9 bacteria had a robust causal relationship with the development of CRC. Among them, Streptococcus thermophilus reduced the risk of CRC; Eubacterium ventriosum and Streptococcus were beneficial bacteria of malignant tumors of colon (CC); Erysipelotrichaceae was a protective factor for malignant tumors of rectal (CR); Bacteroides ovatus was a risk factor for benign tumors. Finally, the mediation analysis revealed 10 pathways by which dietary regulation bacteria affected the risk of CRC, including alcohol consumption increased the risk of CC by reducing the abundance of Eubacterium ventriosum (mediated proportion: 43.044%), and the mediated proportion of other pathways was 7.026%-34.22%.DiscussionThese findings will contribute to the understanding of the different carcinogenic mechanisms of intestinal flora in the colon and rectum and the risk of tumor transformation, thereby aiding CRC prevention, early screening, and the development of future strategies to reduce CRC risk.</p

Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty

Summary: Precocious puberty, a pediatric endocrine disorder classified as central precocious puberty (CPP) or peripheral precocious puberty (PPP), is influenced by diet, gut microbiota, and metabolites, but the specific mechanisms remain unclear. Our study found that increased alpha-diversity and abundance of short-chain fatty acid–producing bacteria led to elevated levels of luteinizing hormone and follicle-stimulating hormone, contributing to precocious puberty. The integration of specific microbiota and metabolites has potential diagnostic value for precocious puberty. The Prevotella genus-controlled interaction factor, influenced by complex carbohydrate consumption, mediated a reduction in estradiol levels. Interactions between obesity-related bacteria and metabolites mediated the beneficial effect of seafood in reducing luteinizing hormone levels, reducing the risk of obesity-induced precocious puberty, and preventing progression from PPP to CPP. This study provides valuable insights into the complex interplay between diet, gut microbiota and metabolites in the onset, development and clinical classification of precocious puberty and warrants further investigation