Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF-κB Activation and Protects against Inflammatory Responses.

The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is critical for cancer cell proliferation and immune cell phenotypes, but whether it can contribute to macrophage inflammatory responses remains unclear. In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/ß-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/ß-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-mediated inflammatory responses.

Synthesis of quinazolinones via Cp*Co(III)-catalyzed C-H functionalization of primary amides with oxadiazolones.

Multi-heteroatom heterocycle synthesis through direct C-H bond activation is methodologically appealing but synthetically challenging. An efficient double C-N bond formation sequence to prepare quinazolinones utilizing primary amides and oxadiazolones in a catalytic redox-neutral [CoCp*(CO)I2]/AgSbF6 system, where oxadiazolone could function as an internal oxidant to maintain the catalytic cycle, is reported. Amide-directed C-H bond activation and oxadiazolone decarboxylation are key to the success of this traceless, atom- and step-economic, and cascade approach for the construction of the quinazolinone skeleton.

Enhancement of Photoluminescence in BaSi2O2N2:Eu2+ by Partial Ge4+ Substitution for Si4+.

Ge4+-doped BaSi2O2N2: Eu2+ phosphors were prepared by a high temperature solid-state reaction method. The phase structure, photoluminescence (PL) properties and PL thermal stability of the as-synthesized samples were investigated. The emission intensity of the Ba(Si0.99Ge0.01)2O2N2: 0.05Eu2+ phosphor was 41.7% greater than that of BaSi2O2N2:0.05Eu2+. When the temperature increased to 150 °C, the emission intensity of Ba(Si0.99Ge0.01)2O2N2:0.05Eu2+ phosphor was 67.0% of the initial value at room temperature. This value was 22.9% greater than that of BaSi2O2N2:0.05Eu2+. The related mechanism has also been explained through the crystal field theory. All these results indicated that the Ge4+-doped BaSi2O2N2:0.05Eu2+ phosphor is a promising material for application in white light emitting diodes.

Human Umbilical Cord Mesenchymal Stem Cells-derived Exosomal lncRNA FAM99B Represses Hepatocellular Carcinoma Cell Malignancy.

Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes (Exo) have been frequently investigated for disease control. This study was designed to explore the effects of hucMSC-Exo carrying lncRNA family with sequence similarity 99-member B (Exo-lncRNA FAM99B) on hepatocellular carcinoma (HCC) cell behaviour. The expression of lncRNA FAM99B in HCC cells was measured by reverse-transcription quantitative polymerase chain reaction. Protein levels of exosomal markers were quantified using western blotting. Flow cytometry analyses were performed to detect surface markers of hucMSCs and to measure the effects of Exo-lncRNA FAM99B on HCC cell cycle progression and cell apoptosis. Nanoparticle tracking analysis was used to measure the particle size of the exosomes. Additionally, cell viability was evaluated using methyl thiazolyl tetrazolium assays, and Transwell assays were performed to measure cell migration and invasion. Xenograft tumor models were established to explore the role of Exo-lncRNA FAM99B in vivo. Experimental results revealed that lncRNA FAM99B was downregulated in HCC cell lines, and low level of FAM99B is associated with poor survival rates in patients with HCC according to bioinformatics analysis. HucMSCs were identified in a good morphology with positively expressed CD105, CD29, and CD44 as well as negatively expressed CD31, CD14, and HLA-DR. High protein levels of exosomal markers (Alix, CD63 and TSG101) identified the existence of HucMSC-Exo. Importantly, the hucMSCs-Exo could enter HCC cells and exerted a suppressive effect on malignant cell activities. Moreover, overexpression of Exo-lncRNA FAM99B enhanced cell cycle arrest and cell apoptosis while suppressing cell viability, migration, and invasion in HCC. Exo-siRNA-FAM99B exerted the opposite effects on HCC cell process. In vivo experiments verified that Exo-lncRNA FAM99B inhibited tumorigenesis in HCC. In summary, lncRNA FAM99B derived from hucMSC-Exo inhibited malignant cellular phenotypes and tumorigenesis in HCC, which might provide a novel therapeutic strategy for HCC treatment.

Research Progress of the UPR Mechanism and its Effect on Improving Foreign Protein Expression.

The unfolded protein response (UPR) is a protective mechanism against endoplasmic reticulum (ER) stress that induces a series of signal transduction pathways to eliminate misfolded proteins. The UPR mechanism is highly conserved in fungi, higher organisms, plants and mammals. The UPR pathway is activated to stabilize ER functions when there are too many unfolded proteins or misfolded proteins in the ER. However, stress continues when ER proteins are stimulated by toxic substances that affect the balance of the UPR pathway, which causes changes in the structure and function of the ER and other organelles. These ultimately disrupt homeostasis in the body and cause pathological reactions that can be fatal. The UPR mechanism has clear effects on stabilizing the protein-folding environment. Dysfunction or disruption of the UPR mechanism is associated with numerous disorders, including neurodegenerative diseases, loss of control of protein secretion, cerebral ischemia and epilepsy, neuropsychiatric diseases, eye diseases, skin diseases, metabolic and inflammatory diseases, atherosclerosis, and heart disease. Thus, characterization of UPR function and its dysfunction has significant importance and has broad application prospects, which make research into the UPR a research hotspot.

Colorectal cancer cell-derived exosomes promote proliferation and decrease apoptosis by activating the ERK pathway.

Exosomes are small microvesicles released by various cells that play important roles in cell-cell communication. Numerous studies show that colorectal cancer (CRC) cell-derived exosomes are involved in the progression of CRC. However, the specific ways and mechanisms of action have not yet been fully clarified. In the present study, we found that, compared to normal colon epithelial cell (NCM460) derived exosomes, CRC cell-Lovo derived exosomes (Lovo-exo) could be more easily taken up by Lovo cells, most likely because of their cell tropism. In addition, Lovo-exo promoted Lovo cell proliferation and inhibited apoptosis, which is associated with an increased activation of the extracellular signal-regulated protein kinase (ERK). Lovo-exo also dramatically increased Lovo tumor cell growth in vivo. Moreover, the intratumoral injection of GW4869 (an exosomes inhibitor) suppressed tumor growth. These results indicate that CRC cell Lovo-derived exosomes may be a messenger for the proliferation requirements of the originating cancer cells, and targeting tumor-derived exosomes may be very promising for tumor treatment.

Identification of dual luminescence centers from a single site in a novel blue-pumped Ca3Sc2Ge3O12:Ce3+ phosphor.

The luminescence spectra of some trivalent rare-earth ions in a garnet host present interesting multisite structures; however, their mechanism is still not fully understood. In this study, for the first time, we directly observed two luminescence centers of Ce3+ at a single site in a novel garnet Ca3Sc2Ge3O12 phosphor. The spectral characteristics of the two luminescence centers were clearly identified using site-selective and time-resolved spectroscopy. Luminescence excitation was observed at 425 nm and 450 nm, corresponding to emissions at 490 (Ce(i)) nm and 530 (Ce(ii)) nm. The decay curves confirmed the existence of energy transfer from Ce(i) to Ce(ii). The potential mechanisms of the multisite luminescence are also discussed. This study gives a new insight into the concentration-dependent red-shift and inhomogeneous broadening of the Ce3+ emission band in the garnet phosphor. The title phosphor showed excellent thermal stability, with more than 90% of the initial intensity at the functioning temperature (323 K). Finally, a white LED lamp was fabricated, which exhibited an excellent color rendering index (82.3) and a proper correlated color temperature (3582 K). These results demonstrate that Ca3Sc2Ge3O12:Ce3+ is highly promising to serve as a blue-pumped phosphor for white LEDs.

A spectrometer with baseline correction and fast pulse pile-up rejection for prompt gamma neutron activation analysis technology.

The prompt gamma neutron activation analysis (PGNAA) technology is an online nondestructive material analysis technology widely used in industries. In order to achieve real-time measurements, the gamma ray count rate should reach 400 kcps. Due to the limitation of the detector's decay time, the signal output from the detector is heavily piled up. Meanwhile, the industrial site has a temperature fluctuation of 0-50 °C, causing the peak drift in the energy spectrum. This paper presents a readout electronic system specified for PGNAA and proposes series of algorithms that are dedicated for the gamma-ray spectrometric system. The system can achieve a count rate of 400 kcps, and it overcomes poor resolution, spectral distortion, and peak position shift, which are caused by pulse pileups and temperature fluctuations.

Photoluminescence properties of a Ce3+ doped Sr3MgSi2O8 phosphor with good thermal stability.

This study mainly reports an investigation about the crystal structure and photoluminescence properties of a Ce3+ doped alkaline earth metal silicate Sr3MgSi2O8. X-ray powder diffraction (XRD) and structure refinement methods are adopted to characterize the phase composition and crystal structure. The excitation/emission spectra and diffuse reflection spectra (DRS) of the title phosphor are measured and the mechanism of concentration quenching as well as thermal quenching are discussed in detail. Results show that the concentration quenching in Sr3MgSi2O8 is due to dipole-dipole interaction energy transfer between Ce3+ ions. The title phosphor has an excellent thermal stability with 90% emission intensity reserve when the temperature rises to 150 °C. The related mechanism is considered to be the thermal ionization effect and an energy level diagram was proposed to show the thermal ionization process.

Discovery of novel solid solution Ca3Si3-x O3+x N4-2x : Eu2+ phosphors: structural evolution and photoluminescence tuning.

Discovery of novel phosphors is one of the main issues for improving the color rendering index (CRI) and correlated color temperature (CCT) of white light-emitting diodes (w-LEDs). This study mainly presents a systematic research on the synthesis, crystal structure variation and photoluminescence tuning of novel (oxy)nitride solid solution Ca3Si3-x O3+x N4-2x : Eu2+ phosphors. XRD refinements show that lattice distortion occurs when x value diverges the optimum one (x = 1). The lattice distortion causes a widening of emission spectrum and an increase of Stokes shift (ΔSS), which leads to a bigger thermal quenching. With decrease of x value, the emission spectrum shows an obvious red-shift from 505.2 to 540.8 nm, which is attributed to the crystal field splitting. The enhanced crystal field splitting also broadens the excitation spectrum, making it possible to serve as the phosphor for near ultraviolet (n-UV) LEDs. A 3-phosphor-conversion w-LED lamp was fabricated with the as-prepared phosphor, which exhibits high CRI (Ra = 85.29) and suitable CCT (4903.35 K). All these results indicate that the Ca3Si3-x O3+x N4-2x : Eu2+ phosphor can serve as the green phosphor for n-UV w-LEDs, with a tunable spectrum by controlling the crystal structure and morphology.

Progesterone regulation of Na/K-ATPase ß1 subunit expression in the mouse uterus during the peri-implantation period.

Luminal closure and embryo apposition are essential for blastocyst attachment during early pregnancy. In our preliminary microarray results (unpublished data), sodium-potassium adenosine triphosphatase (Na/K-ATPase) ß1 (Atp1b1) was highly expressed in mouse uterus on Days 3 and 4 of pregnancy. However, expression and regulation of Atp1b1 in the mammalian uterus during early pregnancy are unknown. Using in situ hybridization, a strong level of Atp1b1 mRNA was detected in luminal epithelial cells on Days 3 and 4 of pregnancy (Day 1 = day of vaginal plug). The expression pattern of FXYD domain-containing ion transport regulator 4 (Fxyd4) was similar to that of Atp1b1. Real-time reverse transcription polymerase chain reaction confirmed the high expression level of Atp1b1 mRNA. Compared with Day 1, the mRNA level of Atp1b1 on Days 3 and 4 increased by 3.5 ± 0.5 and 4.5 ± 0.5 fold, respectively. When the embryo invaded through epithelial cells into the maternal stromal compartment on day 5, Atp1b1 expression decreased to a basal level. Progesterone stimulated Atp1b1 expression by 2.8 ± 1 fold compared with oil in ovariectomized mice at 24 hours after treatment. Expression of Atp1b1 was further upregulated to 4 ± 0.4 fold by estrogen and progesterone. Based on time-course study, progesterone rapidly induced Atp1b1 expression at 6 and 12 hours (13.7 ± 0.5 and 16.6 ± 1.4, respectively); furthermore, this upregulation was blocked by RU486 (progesterone receptor antagonist). Transcription activity of the Atp1b1 promoter was (Day 1 = day of vaginal plug) stimulated by CCAAT/enhancer binding protein beta (Cebpb). In conclusion, Atp1b1 was highly expressed in luminal epithelium during peri-implantation and upregulated by progesterone.

[Analysis of human papillomavirus type 61, 83 and 84 MY fragments and preparation of standard samples].

OBJECTIVE: To investigate the mutations in nucleotide and amino acid level in HPV61, 83 and 84 Shanxi isolates. METHODS: Amplified fragments of HPV61, 83 and 84 from human papillomavirus (Human papillomavirus, HPV) molecular epidemiologic survey of Shanxi Province using HPV consensus primers MY09/11 were cloned in pMD18-T vector, and the plasmids were sequenced, then nucleotide sequences and amino acid sequences were analyzed. RESULTS: HPV61 and HPV83 isolates were consistent with reference strains U31793 and AF151983 in nucleotide sequences; four mutations of nucleotide (C6760T, T6931C, T6951C and C6987A) were found in HPV84 isolate compared with reference strain AF293960, among which C6987A resulted in D441E and the amplified sensitivity of standard sample of HPV61 using primers MY09/11 was higher than that of HPV83 and 84. CONCLUSION: HPV61 and HPV83 isolates were consistent with reference strains, four mutations of nucleotide and one mutation of amino acid were found in HPV84,the amplified sensitivity of standard sample of HPV61 using primers MY09/11 was the highest among those three isolates.