Binuclear Enamino-Oxazolinate Rare-Earth Metal Complexes: Synthesis and Their Catalytic Performance in Isoprene Polymerization.

We have synthesized a series of binuclear rare-earth metal complexes bearing the newly designed enamino-oxazolinate ligands that feature bridging para-phenyl, meta-phenyl, 1,5-naphthalenyl, and 1,5-anthracenyl moieties. NMR and X-ray diffraction analyses confirmed the binuclear structures of the obtained complexes with two enamino-oxazolinate-metal units located at a trans position against the bridged aryl plane. After activation by [Ph3C][B(C6F5)4], all the rare-earth metal complexes served as efficient catalysts for isoprene polymerization, producing polymers with high cis-1,4 regularity (up to 96.1%) and high molecular weight. The steric and electronic effects exerted on the active metal centers, as well as the radius of metal centers, were the major contributing factors for determining both the catalytic activity and cis-1,4-selectivity of the binuclear catalytic systems. Compared to its mononuclear analogue, the binuclear yttrium catalytic system with a para-phenyl bridge exhibited a higher thermostability and catalytic efficiency during polymerization, revealing a special binuclear effect in this binuclear catalytic system.

The U-shaped association between remnant cholesterol and risk of all-cause and cardiovascular deaths in diabetic adults: Findings from NHANES 1999-2018.

BACKGROUND AND AIMS: We aimed to explore the association between remnant cholesterol (RC) level and risks of all-cause and cardiovascular deaths among American diabetic adults. METHODS AND RESULTS: The data of 4,095 diabetic participants from the National Health and Nutrition Examination Survey (1999-2018) were included for analysis. Deaths were ascertained till December 31, 2019. RC level associated with death was assessed on a continuous scale with restricted cubic splines and by pre-defined quartile groups with Cox regression analysis. After a median follow-up of 6.9 years, 1,060 all-cause and 289 cardiovascular deaths occurred. Association between RC and death was U-shaped, and RC level correlated with the lowest risks of both all-cause and cardiovascular deaths was 0.85 mmol/L. After adjusting for confounders, compared with Quartile 3 (0.66-0.93 mmol/L), hazard ratios for all-cause deaths were 1.43 (95%CI 1.18-1.72, P = 0.0002) in Quartile 1 (≤0.47 mmol/L), 1.20 (95%CI 1.00-1.44, P = 0.05) in Quartile 2 (0.47-0.66 mmol/L), and 1.25 (95%CI 1.05-1.49, P = 0.02) in Quartile 4 (>0.93 mmol/L). Higher risk was also observed for cardiovascular deaths in Quartile 1 (HR 1.66, 95%CI 1.15-2.41, P = 0.007), Quartile 2 (HR 1.39, 95%CI 0.97-2.00, P = 0.08), and Quartile 4 (HR 1.54, 95% CI 1.08-2.19, P = 0.02), as compared with Quartile 3. CONCLUSION: In US adults with diabetes, low and high levels of RC were associated with increased risks of all-cause and cardiovascular deaths, and the lowest risk was observed at RC level of 0.85 mmol/L. These findings suggested that maintaining appropriate RC level may help reduce risk of death in diabetic patients.

An Arabidopsis Retention and Splicing complex regulates root and embryo development through pre-mRNA splicing.

Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.

Ultrapure single-band red upconversion luminescence in Er3+ doped sensitizer-rich ytterbium oxide transparent ceramics for solid-state lighting and temperature sensing.

Achieving single-band upconversion (UC) is a challenging but rewarding approach to attain optimal performance in diverse applications. In this paper, we successfully achieved single-band red UC luminescence in Yb2O3: Er transparent ceramics (TCs) through the utilization of a sensitizer-rich design. The Yb2O3 host, which has a maximum host lattice occupancy by Yb3+ sensitizers, facilitates the utilization of excitation light and enhances energy transfer to activators, resulting in improved UC luminescence. Specifically, by shortening the ionic spacing between sensitizer and activator, the energy back transfer and the cross-relaxation process are promoted, resulting in weakening of green energy level 4S3/2 and 2H11/2 emission and enhancement of red energy level 4F9/2 emission. The prepared Yb2O3: Er TCs exhibited superior optical properties with in-line transmittance over 80% at 600 nm. Notably, in the 980nm-excited UC spectrum, green emission does not appear, thus Yb2O3: Er TCs exhibit ultra-pure single band red emission, with CIE coordinates of (0.72, 0.28) and color purity exceeding 99.9%. To the best of our knowledge, this is the first demonstration of pure red UC luminescence in TCs. Furthermore, the luminescent intensity ratio (LIR) technique was utilized to apply this pure red-emitting TCs for temperature sensing. The absolute sensitivity of Yb2O3: Er TCs was calculated to be 0.319% K-1 at 304 K, which is the highest level of optical thermometry based on 4F9/2 levels splitting of Er3+ known so far. The integration between pure red UC luminescence and temperature sensing performance opens up new possibilities for the development of multi-functional smart windows.

Repurposed major urinary protein pheromones and adult sensory neurons: roles in neuron plasticity and experimental diabetes.

Major urinary proteins (MUPs), members of the broader lipocalin protein family, are classified as pheromones that are excreted in male rodent urine to define conspecific territoriality. In screening for differentially regulated mRNA transcripts in a mouse model of type 1 experimental diabetes mellitus (DM), we identified an unexpected upregulation of several closely related MUP transcripts within diabetic sensory dorsal root ganglia (DRG). Both sexes expressed overall MUP protein content as identified by an antibody widely targeting these upregulated family members, and immunohistochemistry identified expression within neurons, satellite glial cells, and Schwann cells. In dissociated adult sensory neurons, knockdown by an siRNA targeting upregulated MUP mRNAs, enhanced neurite outgrowth, indicating a growth-suppressive role, an impact that was synergistic with subnanomolar insulin neuronal signaling. While MUP knockdown did not generate rises in insulin signaling transcripts, the protein did bind to several mitochondrial and glial targets in DRG lysates. Analysis of a protein closely related to MUPs but that is expressed in humans, lipocalin-2, also suppressed growth, but its impact was unrelated to insulin. In a model of chronic type 1 DM, MUP siRNA knockdown improved electrophysiological and behavioral abnormalities of experimental neuropathy. MUPs have actions beyond pheromone signaling in rodents that involve suppression of growth plasticity of sensory neurons. Its hitherto unanticipated actions overlap with those of lipocalin-2 and may identify a common and widely mediated impact on neuron growth properties by members of the lipocalin family. Knockdown of MUP supports the trophic actions of insulin as a strategy that may improve features of type 1 experimental diabetic neuropathy.NEW & NOTEWORTHY New molecular mechanisms are important to unravel and understand diabetic polyneuropathy, a disorder prevalent in over half of persons with diabetes mellitus (DM). MUPs, members of the lipocalin family of molecules, have an unexpected impact on the plasticity of sensory neurons that are targeted in type 1 experimental diabetic neuropathy. This work explores this potential target in neuropathy in the context of the lipocalin family of molecules.

Production of indole and hydrogen sulfide by the oxygen-tolerant mutant strain Clostridium sp. Aeroto-AUH-JLC108 contributes to form a hypoxic microenvironment.

In this study, the oxygen-tolerant mutant strain Clostridium sp. Aeroto-AUH-JLC108 was found to produce indole when grown aerobically. The tnaA gene coding for tryptophanase responsible for the production of indole was cloned. The tnaA gene from Aeroto-AUH-JLC108 is 1677 bp and has one point mutation (C36G) compared to the original anaerobic strain AUH-JLC108. Phylogenetic analyses based on the amino acid sequence showed significant homology to that of TnaA from Flavonifractor. Furthermore, we found that the tnaA gene also exhibited cysteine desulfhydrase activity. The production of hydrogen sulfide (H2S) was accompanied by decrease in the amount of the dissolved oxygen in the culture medium. Similarly, the amount of indole produced by strain Aeroto-AUH-JLC108 obviously decreased the oxidation-reduction potential (ORP) in BHI liquid medium. The results demonstrated that production of indole and H2S helped to form a hypoxic microenvironment for strain Aeroto-AUH-JLC108 when grown aerobically.

Fermentation of soymilk by Lactobacillus acidipiscis isolated from Chinese stinky tofu capable of efficiently biotransforming isoflavone glucosides to dihydrodaidzein and dihydrogenistein.

BACKGROUND: The soy isoflavone microbial metabolites dihydrodaidzein (DHD), dihydrogenistein (DHG), equol and 5-hydroxy-equol are generally more biologically active than their precursors daidzein and genistein. Bacteria responsible for isoflavone metabolism have been isolated and identified. Fermented soymilk is a potential functional food; however, there are few lactic acid bacteria capable of metabolizing soy isoflavones. RESULTS: A newly isolated Gram-positive facultative anaerobic bacterium, which was named Lactobacillus acidipiscis HAU-FR7, was isolated from the traditional Chinese fermented soy product 'stinky tofu'. Bacterium strain HAU-FR7 can grow under aerobic conditions and can also convert most of the daidzin and genistin in soymilk into DHD and DHG, respectively. The concentrations of DHD and DHG produced were 183 and 134 µmol L-1 , respectively, after fermentation for 24 h. Strain HAU-FR7 does not produce the biogenic amines cadaverine, putrescine, histamine or tyramine, and an antibiotic susceptibility test showed that HAU-FR7 is sensitive to nine of the ten tested antibiotics, except for vancomycin. Moreover, the 1,1-diphenyl-2- picrylhydrazyl free radical scavenging capacity of soymilk fermented with HAU-FR7 was significantly higher than that of unfermented soymilk. CONCLUSION: A facultative anaerobic lactic acid bacterium, designated Lactobacillus acidipiscis HAU-FR7, is capable of reducing the soy isoflavone glucosides daidzin and genistin in soymilk to DHD and DHG efficiently, even in the presence of atmospheric oxygen. The biotransformation activity of HAU-FR7 grown in soymilk is higher than that in de Man-Rogosa-Sharpe liquid culture medium. © 2022 Society of Chemical Industry.

P300/CBP-associated factor (PCAF) attenuated M1 macrophage inflammatory responses possibly through KLF2 and KLF4.

Macrophages exhibit distinct phenotypes in response to environmental signals. The polarization of M1 macrophages plays an essential role in the inflammatory response. However, the specific molecular mechanisms regulating the inflammatory response during M1 macrophage polarization remain to be further understood. Here, we found that the histone acetyltransferase P300/CBP-associated factor (PCAF) was a potential negative regulator of the M1 macrophage inflammatory response. During M1 macrophage polarization, the inflammatory response gradually reduced, but PCAF expression increased. Furthermore, the overexpression of PCAF significantly inhibited the expression of the M1 macrophage-related pro-inflammatory genes TNF-α, IL-6 and CXCL10, while PCAF deficiency enhanced the expression of these genes. Furthermore, we found that PCAF overexpression suppressed the NF-κB signaling pathway and promoted the expression of the Krüppel-like factors (KLF) KLF2 and KLF4 through regulating their transcriptional levels. In addition, KLF2 and KLF4 deficiency reversed the PCAF-induced inhibition of the expression of pro-inflammatory genes in M1 macrophages. Collectively, the present results demonstrate a potential negative regulatory mechanism of the inflammatory response during M1 macrophage polarization and propose a novel mechanism of inflammation resolution for maintaining homeostasis.

Human endogenous retrovirus W family envelope protein (HERV-W env) facilitates the production of TNF-α and IL-10 by inhibiting MyD88s in glial cells.

Human endogenous retrovirus W family envelope protein (HERV-W env) is associated with several neurological and psychiatric disorders, including multiple sclerosis (MS) and schizophrenia. Clinical studies have demonstrated a common link between inflammatory abnormalities and HERV-W env in neuropsychiatric diseases. Nonetheless, the molecular mechanisms by which HERV-W env mediates neuroinflammation are still unclear. In this study, we found that HERV-W env significantly increased the mRNA and protein levels of TNF-α and IL-10 in U251 and A172 cells. HERV-W env also induced a notable increase in Toll-like receptor 4 (TLR4). Knockdown of TLR4 impaired the expressions of TNF-α and IL-10 induced by HERV-W env. Overexpression of HERV-W env led to the upregulation of MyD88 but caused a decrease in MyD88s. MyD88s overexpression suppressed the expressions of TNF-α and IL-10 induced by HERV-W env. These findings indicate that HERV-W env upregulates the expressions of IL-10 and TNF-α by inhibiting the production of MyD88s in glial cells. This work sheds light on the immune pathogenesis of HERV-W env in neuropsychiatric disorders.

LINC00943 is correlated with gastric cancer and regulates cancer cell proliferation and chemosensitivity via hsa-miR-101-3p.

BACKGROUND: Non-coding RNAs have emerged as important regulators in human cancers. In this work, we investigated the role of long intergenic non-protein-coding RNA 943 (LINC00943) in gastric cancer (GC). METHODS: LINC00943 expression was evaluated in GC patient tissues and cell lines. In SNU-5 and MKN-45 cells, LINC00943 was knocked down to investigate its roles in regulating GC cell proliferation, 5-FU chemosensitivity and in vivo explant growth. Possible downstream target of LINC00943, human mature microRNA-101-3p (hsa-miR-101-3p) was also evaluated. RESULTS: LINC00943 was aberrantly overexpressed in in situ GC tumors and immortal GC cell lines. LINC00943 overexpression was associated with GC patients' poor prognosis. LINC00943 knockdown reduced GC cell proliferation, 5-FU resistance and in vivo explant growth. Hsa-miR-101-3p was found to be regulated by LINC00943 in GC. Hsa-miR-101-3p downregulation reversed the tumor-suppressing functions of LINC00943 knockdown in GC cells. CONCLUSION: In summary, our results indicated that LINC00943 was correlated with gastric cancer and regulates cancer cell proliferation and chemosensitivity via hsa-miR-101-3p.

Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.

AtBUD13 affects pre-mRNA splicing and is essential for embryo development in Arabidopsis.

Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing.

Regulation of flowering transition by alternative splicing: the role of the U2 auxiliary factor.

Flowering transition is regulated by complex genetic networks in response to endogenous and environmental signals. Pre-mRNA splicing is an essential step for the post-transcriptional regulation of gene expression. Alternative splicing of key flowering genes has been investigated in detail over the past decade. However, few splicing factors have been identified as being involved in flowering transition. Human heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) consists of two subunits, U2AF35 and U2AF65, and functions in 3' splice site recognition in mRNA splicing. Recent studies reveal that Arabidopsis U2AF65a/b and U2AF35a/b play important roles in the splicing of key flowering genes. We summarize recent advances in research on splicing-regulated flowering transition by focusing on the role of Arabidopsis U2AF in the splicing of key flowering-related genes at ambient temperature and in the abscisic acid signaling pathways.

AtU2AF65b functions in abscisic acid mediated flowering via regulating the precursor messenger RNA splicing of ABI5 and FLC in Arabidopsis.

In mammalians and yeast, the splicing factor U2AF65/Mud2p functions in precursor messenger RNA (pre-mRNA) processing. Arabidopsis AtU2AF65b encodes a putative U2AF65 but its specific functions in plants are unknown. This paper examines the function of AtU2AF65b as a negative regulator of flowering time in Arabidopsis. We investigated the expression and function of AtU2AF65b in abscisic acid (ABA)-regulated flowering as well as the transcript abundance and pre-mRNA splicing of flowering-related genes in the knock-out mutants of AtU2AF65b. The atu2af65b mutants show early-flowering phenotype under both long-day and short-day conditions. The transcript accumulation of the flowering repressor gene FLOWERING LOCUS C (FLC) is reduced in the shoot apex of atu2af65b, due to both increased intron retention and reduced transcription activation. Reduced transcription of FLC results, at least partially, from the abnormal splicing and reduced transcript abundance of ABSCISIC ACID-INSENSITIVE 5 (ABI5), which encodes an activator of FLC in ABA-regulated flowering signaling. Additionally, the expression of AtU2AF65b is promoted by ABA. Transition to flowering and splicing of FLC and ABI5 in the atu2af65b mutants are compromised during ABA-induced flowering. ABA-responsive AtU2AF65b functions in the pre-mRNA splicing of FLC and ABI5 in shoot apex, whereby AtU2AF65b is involved in ABA-mediated flowering transition in Arabidopsis.

microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1.

BACKGROUND: Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer. METHODS: qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan-Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial-mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo. RESULTS: Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo. CONCLUSIONS: These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21-LZTFL1-EMT axis might be a promising strategy in breast cancer therapy. TRIAL REGISTRATION: Retrospectively registered.

RETRACTED: TRAF4 promotes endometrial cancer cell growth and migration by activation of PI3K/AKT/Oct4 signaling.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief as panels from Figure 4A appear similar to each other. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Decreased Expression of miR-185 in Serum and Placenta of Patients with Gestational Diabetes Mellitus.

BACKGROUND: The current study aims to investigate the expression of miR-185 in serum and placenta of patients with gestational diabetes mellitus (GDM) and its relationship with insulin resistance. METHODS: The levels of fasting blood glucose (FPG) and fasting insulin (FINS) were measured and the insulin resistance index (HOMA-IR) was calculated. The levels of serum and placental miR-185 were detected by real-time quantitative PCR (qRT-PCR). The relationship between serum and placental miR-185 levels and HOMA-IR was analyzed using Pearson's correlation assay. The diagnostic value of miR-185 was assessed using receiver operating characteristic curve (ROC). RESULTS: Compared with the control group, the serum and placental level of miR-185 was lowest in the severe GDM group and lower in the mild GDM group. Furthermore, the serum levels of FPG, FINS, and HOMA-IR gradually increased in the mild GDM group and the severe GDM group compared to those in the control group. Further study showed that serum and placental miR-185 levels were negatively correlated with HOMA-IR in 156 patients with GDM. ROC analysis showed that the area under the curve (AUC) was 0.927 with the sensitivity and specificity of 0.865 and 0.838, respectively, indicating serum miR-185 could differentiate patients with GDM from controls. CONCLUSIONS: The down-regulation of miR-185 expression in serum and placenta of pregnant women with GDM is negatively correlated with HOMA-IR, suggesting that the decrease of miR-185 may play an important role in the occurrence and development of GDM.

IgG4-related disease with tracheobronchial miliary nodules and asthma: a case report and review of the literature.

BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease that can affect multiple organs of the body. Pulmonary manifestations of IgG4-RD include pulmonary solid nodules, thickening of bronchovascular bundles, interstitial involvement, and ground glass opacities. Here we present a rare case of IgG4-RD with tracheobronchial nodules and review the relevant literature. CASE PRESENTATION: A 52-year-old man was admitted to our hospital with a history of intermittent cough for 27 months and recurrent wheezing for 17 months. He had been diagnosed with asthma prior to admission and was responsive to oral prednisone (30 mg/day, with gradual tapering). Bronchoscopy performed 2 years prior to admission showed tracheal and bronchial mucosal hyperemia, edema, and miliary nodules. Pathological tests showed chronic inflammation with focal lymphocytic infiltration in the bronchial mucosa. The patient had recurrent cough and wheezing after prednisone was stopped or the dose reduced. At the time of admission to our hospital, his serum immunoglobulin G4 (IgG4) level had increased to 7.35 g/L. Following bronchoscopy, the IgG4 expression in the bronchial mucosa was compared with that observed during the last two bronchoscopies. Bronchoscopy performed 7 months prior to admission revealed IgG4+ plasma cell infiltration in the bronchial tissue, with > 10 IgG4+ plasma cells per high power field and an IgG4+/IgG+ cell ratio of > 40%. The current bronchoscopy revealed a decrease in IgG4 expression in the bronchial tissue, probably because of the intermittent prednisone treatment. The case fulfilled the comprehensive clinical diagnostic criteria for IgG4-RD. He received prednisone and azathioprine, and he has never developed recurrence. CONCLUSIONS: Our case exhibited three important clinical indication: First, tracheobronchial miliary nodules could be the presentation of IgG4-related disease. Second, IgG4-related disease with pulmonary involvement has close connection with asthma. Last, IgG4-related disease can be very sensitive to prednisone, the infiltration of IgG4 positive plasma cells decreased after prednisone treatment and symptoms significantly improved in our case. In conclusion, we reported the first case of IgG4-RD presenting with miliary nodules on the tracheal and bronchial tube walls combined with asthma. The findings will further our understanding of the characteristics of IgG4-RD.

3'-Desmethylarctigenin induces G2/M cell cycle arrest and apoptosis through reactive oxygen species generation in hepatocarcinoma cells.

Previous studies have shown that arctigenin is a promising chemopreventive or therapeutic agent against various cancers. However, less is known about anticancer activity of 3'-desmethylarctigenin (3'-DMAG), which is a biotransformed product from arctigenin or arctin. In this study, we compared the anticancer activity of 3'-DMAG with its parent compound arctigenin and demonstrated that 3'-DMAG exerted a more potent inhibitory effect on HepG2 cells than arctigenin. Mechanistically, reactive oxygen species generation played an apical role in 3'-DMAG-induced G2/M cell cycle arrest and apoptosis in HepG2 cells. Furthermore, the Chk2-Cdc25c-Cdc2-cyclin B1 cascade was found to contribute to the cell cycle arrest, whereas the activation of mitochondrial pathway was involved in the cell apoptosis by 3'-DMAG. Additionally, a mouse xenograft hepatocellular carcinoma model was used to evaluate the antitumor effect of 3'-DMAG in vivo, and the results indicated that 3'-DMAG treatment significantly inhibited tumor growth without apparent toxicity. Taken together, 3'-DMAG is highly effective against liver cancer both in vitro and in vivo. The findings of the present study suggest that this compound deserves to be further investigated for its potential anticancer activity.

Physiological investigations of the influences of byproduct pathways on 3-hydroxypropionic acid production in Klebsiella pneumoniae.

Klebsiella pneumoniae can naturally synthesize 3-hydroxypropionic acid (3-HP), 1,3-propanediol (1,3-PD), and 2,3-butanediol (2,3-BD) from glycerol. However, biosynthesis of these industrially important chemicals is constrained by troublesome byproducts. To clarify the influences of byproducts on 3-HP production, in this study, a total of eight byproduct-producing enzyme genes including pmd, poxB, frdB, fumC, dhaT, ilvH, adhP, and pflB were individually deleted from the K. pneumoniae genome. The resultant eight mutants presented different levels of metabolites. In 24-h shake-flask cultivation, the adhP- and pflB-deletion mutants produced 0.41 and 0.44 g/L 3-HP, respectively. Notably, the adhP and pflB double deletion mutant K. pneumoniaeΔadhPΔpflB produced 1.58 g/L 3-HP in 24-h shake-flask cultivation. When K. pneumoniaeΔadhPΔpflB was harnessed as a host strain to overexpress PuuC, a native aldehyde dehydrogenase (ALDH) catalyzing 3-hydroxypropionaldehyde (3-HPA) to 3-HP, the resulting recombinant strain K. pneumoniaeΔadhPΔpflB(pTAC-puuC) (pTAC-puuC is PuuC expression vector) generated 66.91 g/L 3-HP with a cumulative yield of 70.84% on glycerol in 60-h bioreactor cultivation. Additionally, this strain showed 2.3-, 5.1-, and 0.67-fold decrease in the concentrations of 1,3-PD, 2,3-BD, and acetic acid compared with the reference strain K. pneumoniae(pTAC-puuC). These results indicated that the byproducts exerted differential impacts on the production of 3-HP, 1,3-PD, and 2,3-BD. Although combinatorial elimination of byproduct pathways could reprogram glycerol flux, the enzyme 1,3-propanediol oxidoreductase (DhaT) that catalyzes 3-HPA to 1,3-PD and the enzymes ALDHs, especially, PuuC are most pivotal for 3-HP production. This study provides a deep understanding of how byproducts affect the production of 3-HP, 1,3-PD, and 2,3-BD in K. pneumoniae.