Abstract
Microbiota-host interactions play critical roles in colorectal cancer (CRC) progression, however, the underlying mechanisms remain elusive. Here, we uncover that
Fusobacterium nucleatum
(
F. ...nucleatum
) induces a dramatic decline of m
6
A modifications in CRC cells and patient-derived xenograft (PDX) tissues by downregulation of an m
6
A methyltransferase METTL3, contributing to inducation of CRC aggressiveness. Mechanistically, we characterized forkhead box D3 (FOXD3) as a transcription factor for METTL3.
F. nucleatum
activates YAP signaling, inhibits FOXD3 expression, and subsequently reduces METTL3 transcription. Downregulation of METTL3 promotes its target kinesin family member 26B (KIF26B) expression by reducing its m
6
A levels and diminishing YTHDF2-dependent mRNA degradation, which contributes to
F. nucleatum
-induced CRC metastasis. Moreover, METTL3 expression is negatively correlated with
F. nucleatum
and KIF26B levels in CRC tissues. A high expression of KIF26B is also significantly correlated with a shorter survival time of CRC patients. Together, our findings provide insights into modulating human m
6
A epitranscriptome by gut microbiota, and its significance in CRC progression.
Long-period waveguide grating based filters have attracted attention due to their flexible fabrication, a variety of materials and structures, low back reflection, low insertion loss, and excellent ...performance in the tuning range and temperature sensitivity. To our knowledge, for the first time, a two-segment polymer long-period waveguide grating was cascaded to implement a filter with a narrower bandwidth. Experimental results showed that the device had a maximum extinction ratio of 24 dB at 1 577 nm, and the 12 dB bandwidth was 10 nm. The temperature sensitivity of the fabricated device was 1.79 nm/°C.
We propose a simple thermo-optic mode-selective switch based on an asymmetric directional coupler formed with a two-mode waveguide and a single-mode waveguide, where two electrodes heaters are ...deposited, respectively, on the two waveguides. Depending on which heater is turned on, either one of the two modes in the two-mode waveguide can be selectively switched to the single-mode waveguide or vice versa. Our typical experimental device fabricated with polymer material, which has a total length of 16.5 mm, shows extinction ratios higher than ~10 dB in the C-band for both modes. The switching powers for the two modes are 52 and 109 mW, respectively, and the corresponding switching times are 300 and 400 μs. This device could be used in reconfigurable mode-division-multiplexing systems.
We analyze and explore the potential of using a polymer horizontal slot waveguide as light-analyte interactive region to implement a low-cost and highly sensitive liquid refractive index sensor. ...Numerical analysis shows that the optimized polymer horizontal slot waveguide is able to realize high waveguide sensitivity. With the optimized horizontal slot waveguide, polymer liquid refractive index sensors based on Mach-Zehnder interferometer (MZI) and microring resonator (MRR) are then investigated numerically, and the results show that the MZI-based sensor can achieve high sensitivity of 17024nm/RIU and low limit of detection (LOD) of 1.76×10
−6
RIU while the MRR-based sensor can achieve the sensitivity of 177nm/RIU and the LOD of 1.69×10
−4
RIU with a very small footprint. Compared with the sensors employing conventional silicon or silicon nitride vertical slot waveguide, the sensors employing polymer horizontal slot waveguide exhibit comparable performances but simpler and lower fabrication costs.
The acid–base reactions of NNN-tridentate pyrrolyl ligands (HL1: 2,5-bis((pyrrolidin-1-yl)methylene)-1H-pyrrole; HL2: 2,5-bis((piperidino)methylene)-1H-pyrrole) with rare-earth metal tris(alkyl)s, ...Ln(CH2SiMe3)3(THF)2, afforded the corresponding bis(alkyl) complexes L1Ln(CH2SiMe3)2(THF) x (Ln = Sc, x = 0 (1a); Ln = Y, x = 1 (1b); Ln = Lu, x = 1 (1c)), L2Sc(CH2SiMe3)2 (2a), and L2 2Ln2(CH2SiMe3)4 (Ln = Y (2b); Lu (2c)) in moderate to high yields. X-ray diffraction analysis revealed that the scandium complexes 1a and 2a are THF solvent-free monomers where the ligands coordinate to the Sc3+ ion in a κ1:κ2 mode, while the yttrium and lutetium complexes 1b and 1c have the same ligand coordination geometry to that of the scandium complex but are one-THF solvates; complex 2b, however, is a dimer bridged by two anionic L2 fragments that coordinate to the two yttrium ions in mixed η5:η5/κ1:κ1 coordination modes. Upon activation with an organoborate, all these complexes initiated the controlled polymerization of isoprene. In general, complexes 2a–c, bearing ligand L2, exhibited higher activity than the analogous complexes 1a–c, attached to the L1 ligand. Complex 2b, in which the L2 ligand adopts the mixed η5/κ1 coordination mode, showed the highest activity and livingness mode toward the polymerization of isoprene with high cis-1,4-selectivity (94.1%), and both scandium complexes 1a and 2a exhibited high 3,4-selectivity (87%) irrespective of the ligand type; in contrast, the lutetium complexes initiated the atactic isoprene polymerization. The influences of thell ligand structural factors, the coordination solvent, and the central metal ion on the catalytic activity and selectivity are discussed.
Circular RNAs (circRNAs) have been reported to play key roles in the development of various cancers. However, the biological functions and clinical significance of most circRNAs are still elusive. ...The purpose of this study was to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development and its potential value in the clinic.
qRT-PCR was used to verify the expression level of circCDKN2B-AS1. CCK-8, Transwell, and flow cytometry (FCM) assays were performed to detect cellular proliferation, migration, and apoptosis, respectively. A Seahorse XFe96 Analyzer was used to measure glycolysis metabolism level. RNA pull-down, RNA immunoprecipitation (RIP), actinomycin-D addition assays and Western blotting were used to screen and elucidate the potential mechanisms involved. BALB/c nude mice and zebrafish embryos (AB, WT) were used as animal models to investigate tumorigenesis capability.
FDG-microPET/CT imaging and lactic acid (LA) and pyruvic acid (PA) content detection assays were used to detect the level of glucose metabolism in subcutaneous tumors from nude mice.
CircCDKN2B-AS1, a circular isoform of the long noncoding RNA (lncRNA) CDKN2B-AS1, was upregulated in cervical cancer and precancerous tissues. We found that circCDKN2B-AS1 associated with the IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2 (HK2) mRNA, the rate-limiting enzyme of the aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to the 3' untranslated region (UTR) of HK2 mRNA, consequently affecting the malignant cell phenotype and aerobic glycolysis in cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1, lacking the IMP3 binding site, did not have such effects. Utilization of an inhibitory peptide to block the interaction between circCDKN2B-AS1 and the IMP3 protein impeded the binding of IMP3 to the 3'UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells.
Our findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging the IMP3 protein to stabilize HK2 mRNA, consequently promoting the malignant phenotype in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.
Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This ...study aims to evaluate the potential effects of
JYLP-326 on test anxious college students.
Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism.
The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of
and
at the genus level was observed in the placebo group, and the relative abundance of
and
decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms.
The results indicate that the intervention of
JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.
RNA methylation has recently emerged as an important category of epigenetic modifications, which plays diverse physiopathological roles in various cancers. Recent studies have confirmed the presence ...of 5-methylcytosine (m
5
C) modification on mammalian mRNAs, mainly modified by NOP2/Sun RNA methyltransferase family member 2 (NSUN2), but little is known about the underlying functions of m
5
C. Gynecologic cancers are malignancies starting from women’s reproductive organs. The prevalence of gynecologic cancers leads to a massive economic burden and public health concern. In this study, we investigated the potential biological functions of NSUN2 in common gynecologic cancers including cervical cancer, ovarian cancer, and endometrial cancer. Remarkably, distinct scenarios were found. The levels of NSUN2 did not show alteration in endometrial cancer, and in ovarian cancer, depletion of upregulated NSUN2 did not reduce carcinogenesis in cancer cells, suggesting that the upregulated NSUN2 might be an incidental effect. On the contrary, NSUN2 played a role in tumorigenesis of cervical cancer; depletion of upregulated NSUN2 notably inhibited migration and invasion of cancer cells, and only wild-type but not catalytically inactive NSUN2 rescued these malignant phenotypes of cancer cells. Mechanistically, NSUN2 promoted migration and invasion by leading to m
5
C methylation on keratin 13 (
KRT13
) transcripts, and methylated
KRT13
transcripts would be recognized and stabilized by an m
5
C reader, Y-box binding protein 1 (YBX1). Collectively, these results not only displayed the nature of diversity among human malignancies, but also demonstrated a novel NSUN2-dependent m
5
C-YBX1-KRT13 oncogenic regulatory pathway.
Since the trimerization of isocyanate occurs easily and controllably to form a clear trifunctional isocyanate ring, this reaction is an ideal candidate for the synthesis of a clear ...poly(urethane-isocyanurate) network polymer. Poly(urethane-isocyanurate) network polymer (PUI) was prepared from diphenylmethane diisocyanate (MDI) and propylene glycol (PPG) by cyclotrimerization of isocyanate group (NCO). It was proved that the expected product was successfully prepared by NCO determination, fourier transform infrared (FTIR) and gel permeation chromatography (GPC) characterization. The mechanical and thermal properties were characterized. Through the effects of catalyst dosage, polyurethane prepolymer molecular weight, reaction time, reaction temperature and MDI addition on the reaction process, it is determined that under certain other conditions, the step heating method is better for cyclotrimerization reaction. Generally, the better heating conditions are 60 °C/1 h + 80 °C/4 h + 100 °C/2 h + 120 °C/2 h + 140 °C/2 h + 160 °C/2 h. The results of thermogravimetric analysis (TGA) and mechanical properties showed that with the increase of cross-linking points in the polymer structure, the thermal stability, tensile strength, tensile modulus and hardness of PUI increased, while the elongation at break decreased significantly. The glass transition temperature (Tg) of PUI is around 45 °C, and it can be seen that the elastic modulus of the material can range from 58 to 1980 MPa. X-ray diffraction results show that the rubber phase represented by the flexible segment and the plastic phase represented by the rigid structure are amorphous.
Although gut hormone glucagon-like peptide 1 (GLP-1) has been widely used for treating diabetes, the extremely short half-life greatly limits its application. The purpose of this study is to explore ...the effects of an engineered bacteria with expression of GLP-1 on obese mice induced by high fat diet (HFD).
The engineered strain of MG1363-pMG36e-GLP-1 (M-GLP-1) was constructed and its anti-obesity effects were evaluated
. The bodyweight, the morphology of adipose and liver tissue, and liver function were examined. Quantitative RT-PCR and Western blot were used to measure the expressions of the genes involved in fatty acid oxidation synthesis. The intestinal microbial diversity was detected with high-throughput sequencing analysis.
The engineered bacteria could produce GLP-1. It also significantly decreased the bodyweight and improved the glucose intolerance in the obese mice induced by HFD. Moreover, the strain also reduced the triglyceride (TG) in serum, protected liver, as well as decreased the intracellular TG in liver tissues of the obese mice. Furthermore, our results showed that the expressions of the genes including peroxisome proliferator-activated receptors α (PPARα) and its target genes were enhanced in liver tissues when mice treated with M-GLP-1. Finally, we found that the engineered strain markedly increased intestinal microbial diversity.
Our results suggested the genetically engineered bacteria that constitutively secreted GLP-1 could improve obesity and the mechanism may be related to promoting fatty acid oxidation and increasing intestinal microbial diversity of the obese mice.
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