Enhanced interactions among gut mycobiomes with the deterioration of glycemic control.

BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry. FINDINGS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic ß-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. FUNDINGS: This study was supported by MOST and NSFC of China.

Cerebral Blood Flow Alterations and Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Reduction in cerebral blood flow (CBF) plays an essential role in the cognitive impairment and dementia in obesity. However, current conclusions regarding CBF changes in patients with obesity are inconsistent. OBJECTIVE: A systematic review and meta-analysis was performed to evaluate the relationship between obesity and CBF alterations. METHODS: We systematically screened published cross-sectional and longitudinal studies focusing on the differences in CBF between obese and normal-weight individuals. Eighteen studies including 24,866 participants, of which seven articles reported longitudinal results, were evaluated in the present study. RESULTS: The results of the meta-analysis showed that in cross-sectional studies, body mass index (BMI) was negatively associated with CBF (ß= -0.31, 95% confidence interval [CI]: -0.44, -0.19). Moreover, this systematic review demonstrated that obese individuals showed global and regional reductions in the CBF and increased CBF in diverse functional areas of the frontal lobe, including the prefrontal cortex, left frontal superior orbital, right frontal mid-orbital cortex, and left premotor superior frontal gyrus. CONCLUSION: Our findings suggest that BMI, rather than waist circumference and waist-to-hip ratio, is inversely associated with CBF in cross-sectional studies. The CBF of obese individuals showed global and regional reductions, including the frontal lobe, temporal and parietal lobes, cerebellum, hippocampus, and thalamus.

A novel ratiometric fluorescent probe for the detection of uric acid in human blood based on H2O2-mediated fluorescence quenching of gold/silver nanoclusters.

In this work, a ratiometric fluorescent probe (RF-probe) for highly sensitive and selective detection of uric acid was reported for the first time toward H2O2 based on inner filter effect (IFE) between bimetallic gold/silver nanoclusters (Au/Ag NCs) and 2,3-diaminophenazine (DAP). For this RF-probe, uric acid was degraded to allantoin and H2O2. Upon the addition of HRP, o-phenylenediamine (OPD) could be catalytically oxidized to DAP in the presence of H2O2, then the fluorescence intensity corresponding to DAP at 580 nm increased dramatically with a fluorescence quenching of BSA-Au/Ag NCs at 690 nm, resulting in a RF-probe toward uric acid. This RF-probe allowed for the sensitive detection of uric acid in range of 5.0 × 10-6 M to 5.0 × 10-5 M with a detection limit (S/N = 3) as low as 5.1 × 10-6 M. At the same time, it has been successfully used for uric acid levels detection in human serum, and the results are consistent with those of the hospital. RF-probe built may provide a ratiometric fluorescence universal platform for detection of various species involving in the production of H2O2 in other biological systems.

Genome-Wide Analysis of CDPK Family in Foxtail Millet and Determination of SiCDPK24 Functions in Drought Stress.

Plant calcium-dependent protein kinases (CDPKs) were reported to play important roles in plant resistance to abiotic stress. Foxtail millet cultivation "H138" was used for RNA-seq analysis. The data from drought-induced de novo transcriptomic sequences of foxtail millet showed that CDPKs were up- or down-regulated by drought to different degrees. In this study, 29 foxtail millet CDPKs were classified into four subgroups. These genes were unevenly distributed on nine foxtail millet chromosomes, and chromosomes 2, 3, and 9 contained the most SiCDPK members. Analysis of putative cis-acting elements showed that most foxtail millet CDPK genes contained the ABRE, LTR, HSE, MYB, MYC, DRE, CGTCA-motif, and TGACG-motif cis-acting elements, which could be activated by abiotic stresses. Real-time PCR analysis indicated that 29 SiCDPK genes experienced different degrees of induction under drought and ABA stresses. SiCDPK24 had the highest expression levels at 6 and 12 h of drought treatment and was chosen for further analysis. SiCDPK24 localized to the cell membrane and the nucleus of Arabidopsis mesophyll protoplasts. Western blot analysis showed that SiCDPK24 protein had autophosphorylation activity. Overexpression of SiCDPK24 in Arabidopsis enhanced drought resistance and improved the survival rate under drought stress. It also activated the expressions of nine stress-related genes, namely RD29A, RD29B, RD22, KIN1, COR15, COR47, LEA14, CBF3/DREB1A, and DREB2A. These genes are involved in resistance to abiotic stresses in Arabidopsis. These results indicate that foxtail millet CDPK genes play important roles in resisting drought stress.

Hippo signaling pathway in lung development, regeneration, and diseases.

function between the circulation and the atmospheric environment. Lung diseases, including lung cancer, are among the leading causes of death in the modern society. Research on lung development, regeneration and cancer could provide significant insights for the development of therapeutic approaches on lung diseases. Hippo/YAP/TAZ signaling pathway regulates cell proliferation and differentiation, controls organ size, and plays an important role in response to mechanical forces. YAP/TAZ are expressed in many cell types and serve various regulatory functions in the embryonic and adult lungs. In this review, we mainly focus on the roles of Hippo/YAP/TAZ signaling pathway in embryonic lung development, regeneration and cancer. We postulate that Hippo/YAP/TAZ signaling may play potential roles in regulating the alveolar mechanics and immune responses in the lung.

[Relationship between TIM-4 polymorphism and childhood asthma].

OBJECTIVE: To elucidate whether the polymorphism of asthma immune regulator gene TIM-4 is associated with the risk of childhood allergic asthma in the southwest region of China. METHODS: TIM-4 gene promoter region RS6882076 and intron RS4704727 were studied. PCR-RFLP was used to test the genotypes of two polymorphism loci among 579 cases (average 7.2 years old) of asthma and 524 controls (average 7.6 years old) in a case-control study. RESULTS: There were significant differences in the frequency of gene types at RS4704727 site between the asthma and the control groups (P<0.01). The results of PCR-RFLP showed that the polyporphisms of RS6882076 and RS4704727 in TIM-4 gene were present in this study population. The frequency of T allele at the RS4704727 site in the asthma group was significantly lower than that in the control group (OR=1.603; 95%CI 1.304-1.971; P<0.01). There were no significant differences in the frequencies of gene types and allele at RS6882076 site between the two groups (P>0.05). CONCLUSIONS: RS4704727 polymorphism of TIM-4 gene may be associated with childhood asthma, providing a better understanding of the pathogenesis of childhood asthma in the Southwest region of China.