TIGAR Protects Against Adenine-Induced Ferroptosis in Human Proximal Tubular Epithelial Cells by Activating the mTOR/S6KP70 Axis.

TP53-induced glycolysis and apoptosis regulator (TIGAR) acts as a switch for nephropathy, but its underlying mechanism is still unclear. The purpose of this study was to explore the potential biological significance and underlying mechanism of TIGAR in modulating adenine-induced ferroptosis in human proximal tubular epithelial (HK-2) cells. HK-2 cells under- or overexpressing TIGAR were challenged with adenine to induce ferroptosis. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were assayed. Expression of ferroptosis-associated solute carrier family seven-member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) at the level of mRNA and protein were measured by quantitative real-time-PCR and western blotting. The phosphorylation levels of proteins in the mTOR/S6KP70 pathway were determined by western blotting. Adenine overload triggered ferroptosis in HK-2 cells, as evidenced by reduced levels of GSH, SLC7A11, and GPX4, and increased levels of iron, MDA, and ROS. TIGAR overexpression repressed adenine-induced ferroptosis and induced mTOR/S6KP70 signaling. Inhibitors of mTOR and S6KP70 weakened the ability of TIGAR to inhibit adenine-induced ferroptosis. TIGAR inhibits adenine-induced ferroptosis in human proximal tubular epithelial cells by activating the mTOR/S6KP70 signaling pathway. Therefore, activating the TIGAR/mTOR/S6KP70 axis may be a treatment for crystal nephropathies.

[Mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease based on GC-MS and network pharmacology].

To study the material basis and mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease(AD) based on GC-MS and network pharmacology. Ingredients of volatile oil from A.oxyphylla were analyzed by GC-MS. Targets of those ingredients were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Relevant targets of AD were obtained through such databases as DrugBank, STITCH, OMIM. Intersection targets of ingredients and diseases were obtained by Online Venny map, and PPI network was established by STRING to screen out core targets. Gene ontology(GO) functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID. The "ingredients-target-pathway" network was constructed by software Cytoscape 3.8.1 to screen out potential active ingredients of volatile oil from A.oxyphylla in the treatment of AD. The results showed that a total of 6 active ingredients were screened from the volatile oil of A.oxyphylla by GC-MS, 17 targets corresponding to 6 active ingredients were found in TCMSP database, and 3 448 AD targets were found in DrugBank database. "Ingredients-target-pathway" network and PPI network showed there were 4 potential active ingredients in the treatment of AD and 4 core targets. GO analysis and KEGG analysis showed 34(P<0.05) and 5(P<0.05) pathways, respectively, including nerve ligand receptor interaction, calcium signaling pathway, cholinergic synapse and 5-hydroxytryptaminergic synapse. This suggested that volatile oil from A.oxyphylla could synergistically treat AD by regulating calcium balance, cholinergic balance and phosphorylation. This study provided reference and guidance for further study of volatile oil from A.oxyphylla in the treatment of AD.

Marinobacter denitrificans sp. nov., isolated from marine sediment of southern Scott Coast, Antarctica.

A novel bacterium, designated JB02H27T, was isolated from marine sediment collected from the southern Scott Coast, Antarctica. Cells were Gram-stain-negative, facultatively anaerobic, polar-flagellated and motile rods. Growth occurred at 4-45 °C, at pH 7.0-9.0 and with 3-25 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain JB02H27T consistently fell within the genus Marinobacter and formed a clade together with Marinobacter algicola DG893T (98.8 % similarity), Marinobacter confluentis KCTC 42705T (98.4 %), Marinobacter salarius R9SW1T (98.4%) and Marinobacter halotolerans CP12T (97.9 %), which were subsequently used as reference strains for comparisons of phenotypic and chemotaxonomic characteristics. Average nucleotide identity values between strain JB02H27T and the four related type strains were 80.9, 76.6, 81.9 and 76.3 %, respectively. The major fatty acids were summed feature 3, C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids included phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and an unidentified phospholipid, aminolipid, aminophospholipid and glycolipids. The sole respiratory quinone was ubiquinone-9. The DNA G+C content was 56.9 mol%. Based on the genomic, phylogenetic, phenotypic and chemotaxonomic analysis, we propose that strain JB02H27T represents a novel species of the genus Marinobacter, for which the name Marinobacter denitrificans sp. nov. is proposed. The type strain is JB02H27T (=GDMCC 1.1528T=KCTC 62941T).

Tumor-suppressor Fbxw7 targets SIK2 for degradation to interfere with TORC2-AKT signaling in pancreatic cancer.

The tumor suppressor F-box/WD repeat-containing protein 7 (Fbxw7) is a substrate-recognition subunit of a ubiquitin ligase complex. We have previously proposed that Fbxw7 inhibited pancreatic cancer cell proliferation and invasion by targeting ß-catenin. To identify other targets of Fbxw7 involved in pancreatic carcinogenesis, we screened the human protein database for Fbxw7 target candidates using the conserved Fbxw7-recognizing sequences. Twenty-three candidates are identified, including five known Fbxw7 targets and two cancer-related genes (salt inducible kinase 2 [SIK2] and ZMIZ1). We identified SIK2 as an Fbxw7 target for degradation by binding to the "TPPPS" motif of SIK2 in pancreatic cancer cells. We also demonstrated that SIK2 promoted proliferation and mitotic progression of pancreatic cancer cells. Moreover, endogenous Fbxw7 downregulates SIK2 protein level for controlling cell cycle progression, possibly by interfering the SIK2/TORC2/AKT signaling pathway to modulate p21 expression. Collectively, these data demonstrate that Fbxw7 targets the cell cycle controller, SIK2, for degradation, thereby leading to the disruption of downstream TORC2/AKT signaling to inhibit pancreatic cancer cell proliferation and cell cycle progression.

[Effect of Sijunzi Decoction on regulation of Aß-related proteins across blood-brain barrier].

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aß_(25-35) oligomers(final concentration 40 µmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aß_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aß-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 µmol·L~(-1) Aß_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aß_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aß_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aß_(25-35) transport across the blood-brain barrier.

A greener catalyst for hydroboration of imines-external electric field modify the reaction mechanism.

Usually, an extra catalyst (for example, the transition metal complexes) need to be used in catalyzing hydroboration, which involved the cost, environment, and so forth. Here, a greener and controllable catalyst-external electric field (EEF) was used to study its effect on hydroboration of N-(4-methylbenzyl)aniline (PhN═CHPhMe) with pinacolboane (HBPin). The results demonstrated that EEF could affect the barrier heights of both two pathways of this reaction. More significantly, flipping the direction of EEF could modify the reaction mechanism to induce a dominant inverse hydroboration at some field strength. That is to say, oriented EEF is a controlling switch for the anti- or Markovnikov hydroboration reaction of imines. This investigation is meaningful for the exploration of greener catalyst for chemistry reaction and guide a new method for the Markovnikov hydroboration addition. © 2019 Wiley Periodicals, Inc.

Lysobacter penaei sp. nov., isolated from intestinal content of a Pacific white shrimp (Penaeus vannamei).

The polyphasic taxonomic approach was used to characterize a novel bacteria strain, designated SG-8T, which was isolated from intestinal content of a Pacific white shrimp (Penaeus vannamei). Cells were Gram-stain-negative, aerobic, non-gliding rods. Growth occurred at 10-45 °C (optimum, 20-30 °C), pH 5.0-10.0 (optimum, 6.0-7.0) and in 0-6.0 % (w/v) NaCl (optimum, 0-4.0 %). The 16S rRNA gene sequence of strain SG-8T showed the highest sequence similarity to Lysobacter maris KMU-14T (98.6 %). On phylogenetic trees, strain SG-8T formed a stable cluster with Lysobacter maris KMU-14T, Lysobacter alkalisoli SJ-36T, Lysobacter spongiae 119BY6-57T and Lysobacter aestuarii S2-CT. The average nucleotide identity and digital DNA-DNA hybridization values between strain SG-8T and the four reference type strains listed above were 83.3, 82.3, 83.5, 83.3% and 22.8, 22.7, 22.7, 22.9 %, respectively. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 9 (iso-C17 : 1 ω9c and/or 10-methyl C16 : 0), iso-C16 : 0, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), iso-C17 : 0, iso-C11 : 0 3OH and iso-C11 : 0. Ubiquinone-8 (Q-8) was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The DNA G+C content was 68.8 mol%. Based on the results of genomic, phylogenetic, phenotypic and chemotaxonomic analyses, strain SG-8T represents a novel species of the genus Lysobacter, for which the name Lysobacter penaei sp. nov. is proposed. The type strain is SG-8T (=GDMCC 1.1817T=KACC 21942T).

Antarcticibacterium flavum gen. nov., sp. nov., isolated from marine sediment.

A Gram-stain-negative, strictly aerobic, yellow-pigmented, non-gliding, oval to rod-shaped bacterial strain, designated JB01H24T, belonging to the family Flavobacteriaceae, was isolated from marine surface sediment collected from the Ross Sea, Antarctica. Strain JB01H24T grew at 4-40 °C (optimum 25-30 °C), pH 7.0-9.0 (optimum 7.5-8.0), and in the presence of 0-8 % NaCl (optimum 3 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain JB01H24T formed an independent linkage within the family Flavobacteriaceae and was closely related with the genus Gillisia. Strain JB01H24T exhibited 16S rRNA gene sequence similarities of 95.3-91.5 % and 94.9-94.0 % to the type strains of the genera Gillisia and Salinimicrobium, respectively. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), anteiso-C15 : 0, iso-C15 : 1 G and summed feature 9 (iso-C17 : 1ω9c and/or 10-methyl C16 : 0). The major polar lipids were phosphatidylethanolamine, seven unidentified lipids, two unidentified aminolipids and an unidentified aminophospholipid. Strain JB01H24T contained menaquinone-6 as the only ubiquinone. The DNA G+C content was 42.4 mol%. On the basis of phylogenetic, physiological and chemotaxonomic properties, strain JB01H24T is considered to represent a novel species of a new genus within the family Flavobacteriaceae, for which the name Antarcticibacterium flavum gen. nov., sp. nov. is proposed. The type strain of Antarcticibacterium flavum is JB01H24T (=GDMCC 1.1229T=KCTC 52984T).

Gramella antarctica sp. nov., isolated from marine surface sediment.

A Gram-stain-negative, aerobic, yellow-coloured, motile by gliding, rod-shaped bacterial strain, designated R17H11T, was isolated from surface sediment collected from the Ross Sea, Antarctica. Growth optimally occurred at 25-30 °C, at pH 7.0-7.5 and in the presence of 3 % NaCl (w/v). Phylogenetic trees based on 16S rRNA gene sequences indicated that strain R17H11T clustered together with Gramella flava JLT2011T and fell within the genus Gramella. Strain R17H11T shared the highest 16S rRNA gene similarities (96.1 and 96.0 %) with the type strains of Gramella forsetii and G. flava, and 92.6-95.5 % similarities with those of other known Gramella species. Strain R17H11T contained menaquinone-6 as the only isoprenoid quinone. The major fatty acids (>5 %) were summed feature 3 (17.5 %, comprising C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 (14.0 %), summed feature 9 (11.8 %, comprising 10-methyl C16 : 0 and/or iso-C17 : 1ω9c), iso-C17 : 0 3-OH (11.8 %), iso-C16 : 0 (7.4 %), C17 : 1ω6c (6.9 %) and anteiso-C15 : 0 (5.1 %). The major polar lipids were phosphatidylethanolamine, four unidentified lipids, an unidentified aminolipid, an unidentified aminophospholipid and an unidentified glycolipid. The DNA G+C content of strain R17H11T was 38.6 mol%. On the basis of the phylogenetic, physiological and chemotaxonomic characteristics, strain R17H11T represents a novel species in the genus Gramella, for which the name Gramellaantarctica sp. nov. is proposed. The type strain of the novel species is R17H11T (=GDMCC 1.1208T=KCTC 52925T).

Arenibacter catalasegens sp. nov., isolated from marine surface sediment, and emended description of the genus Arenibacter.

A Gram-staining-negative, aerobic, non-motile, rod-shaped bacterium, designated as P308H10T, was isolated from surface sediment of the Southern Indian Ocean. Growth occurred at 4-36 °C (optimum 20-25 °C), pH 6.0-8.5 (optimum 7.5-8.0) and in the presence of 1-8 % (w/v) NaCl (optimum 2-3 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain P308H10T lies within the clade of members of the genus Arenibacter and is closely related to Arenibacterhampyeongensis HP12T (98.0 %), Arenibacterechinorum KMM 6032T (98.4 %), Arenibacterpalladensis LMG 21972T (97.9 %), Arenibactertroitsensis KMM 3674T (97.9 %) and 'Arenibacter algicola' TG409 (98.1 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain P308H10T and the five reference strains were 85.9-80.6 % and 30.2-23.6 %, respectively. The major fatty acids (>10 %) of strain P308H10T were summed feature 3, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0. The major polar lipids comprised phosphatidylethanolamine, five unidentified aminolipids and four unidentified lipids. The only respiratory quinone was menaquinone-6. The genomic DNA G+C content was 38.2 mol%. On the basis of the phenotypic, phylogenetic and chemotaxonomic data presented, strain P308H10T represents a novel species of the genus Arenibacter, for which the name Arenibacter catalasegens sp. nov. is proposed. The type strain is P308H10T (=GDMCC 1.1230T=KCTC 52983T). An emended description of the genus Arenibacter is also proposed.

Possible B-C bonding in the hydroboration of benzonitrile by an external electric field.

Generally, the hydroboration of benzonitrile produces B-N containing compounds. However, an unprecedented B-C bond may be formed in the presence of a suitable external electric field (EEF). In reactions of benzonitrile with borane, when the EEF is oriented parallel to the positive direction (N → C) of the N[triple bond, length as m-dash]C bond, the barriers to Markovnikov hydroboration are decreased gradually, meaning the pathway for generating B-C bonds becomes more favorable. Accordingly, hydroboration could be influenced and its selectivity could be controlled by changing the magnitude and direction of an applied EEF.

Aurantimonas aggregata sp. nov., isolated from deep-sea sediment.

A novel bacterium, designated R14M6T, was isolated from deep-sea sediment collected from the Ross Sea, Antarctica. Cells are Gram-stain-negative, aerobic, pale yellow, short-rod-shaped, polar-flagellated and aggregate-forming. Growth occurs at 4-36 °C, pH 6.0-8.3, and in 1-15 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain R14M6T clustered together with Aurantimonas endophytica EGI6500337T and fell within the genus Aurantimonas. The 16S rRNA gene sequence of strain R14M6T shared similarity with A. endophytica EGI6500337T (99.15 %), A. manganoxydans DSM 21871T (97.73 %), A. coralicida DSM 14790T (97.58 %) and 'A. litoralis' KCTC 12094 (97.51 %). The DNA-DNA relatedness values between strain R14M6T and A. endophytica EGI6500337T, A. coralicida DSM 14790T, A. manganoxydans DSM 21871T and 'A. litoralis' KCTC 12094 were 36.9±4.5, 27.6±2.8, 29.6±1.2 and 25.2±2.4 % respectively. The major fatty acid of strain R14M6T was C18 : 1ω7c. The major polar lipids were phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified aminolipid. Strain R14M6T contained Q-10 as the dominant isoprenoid quinone. The DNA G+C content of strain R14M6T was 67.4 mol%. Based on the phylogenetic, physiological and chemotaxonomic analyses, strain R14M6T represents a novel species of the genus Aurantimonas, for which the name Aurantimonas aggregata sp. nov. is proposed. The type strain is R14M6T (=GDMCC 1.1202T=KCTC 52919T).

Arenibacter antarcticus sp. nov., isolated from marine sediment.

A strictly aerobic, Gram-stain-negative, pale-golden, rod-shaped bacterium, designated as R18H21T, was isolated from marine sediment collected from the Ross Sea, Antarctica. Strain R18H21T grew at 4-40 °C (optimum 25 °C), at pH 6.3-9.2 (optimum 7.5-8.5) and in 0.5-6 % (w/v) NaCl (optimum 2 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain R18H21T belonged to the genus Arenibacter, with the highest similarity to two type strains, Arenibacter latericius KMM 426T (96.6 %) and Arenibacter certesii KMM 3941T (96.6 %), and lower similarities (95.2-95.9 %) to five other members of the genus Arenibacter. The major fatty acids were iso-C17 : 0 3-OH, Summed Feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C15 : 0, iso-C15 : 1 G. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified phospholipid. The respiratory quinone of strain R18H21T was menaquinone-6. The DNA G+C content was 40.0 mol%. Based on phylogenetic, physiological and chemotaxonomic features, strain R18H21T has been classified as a novel species in the genus Arenibacter, for which the name Arenibacterantarcticus sp. nov. is proposed. The type strain of the novel species is R18H21T (=GDMCC 1.1159T=KCTC 52924T).

Bacterial contamination of medical uniforms: a cross-sectional study from Suzhou city, China.

Few studies have been conducted which evaluate the prevalence of contamination of medical uniforms in China. The present study was designed to explore the characteristics of uniform contamination and associated factors. A total of 120 participants were enrolled in the study and 122 uniforms were sampled. Each uniform was sampled at three different sites to determine the colonisation of microorganisms. A total of 366 swab samples were cultured; 294 (80.3%) samples yielded various microorganisms and 75(61.5%) uniforms were contaminated with bacteria. The uniforms of medical students had the highest prevalence of contamination. The cuffs of uniforms were the most easily infected with bacteria. Participants who wiped their hands at the back of uniforms had higher contamination rate in the hanging part of uniforms. Our study demonstrated that medical uniforms can harbour microorganisms. Proper handling of medical uniforms and adequate education to medical staffs are required to decrease healthcare-associated infections.

Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors.

Two groups of novel hydroxypyridinone derivatives 6(a-e) and 12(a-c), were designed as potential tyrosinase inhibitors, and synthesized using kojic acid as a starting material. The tyrosinase inhibitory activity of these two groups was demonstrated to be potent, especially compounds 6e and 12a, whose IC50 values for monophenolase activity were 1.95µM and 2.79µM, respectively. Both of these values are lower than that of kojic acid (IC50=12.50µM). Compounds 6e and 12a were investigated for the inhibitory effect on diphenolase activity. The results showed that the inhibitory mechanism of these two compounds was reversible and that the inhibitory type was a competitive-uncompetitive mixed-type. The values of IC50 of 6e and 12a on the diphenolase activity of tyrosinase were determined to be 8.97µM and 26.20µM, respectively. The inhibitory constants (KI and KIS) of 6e were determined as 17.17µM and 22.09µM, respectively; and the KI and KIS values of 12a were 34.41µM and 79.02µM, respectively. Compound 6e showed a greater ability to reduce copper and a stronger copper chelating ability than kojic acid.

Lack of association between COX-2 8473T>C polymorphism and breast cancer risk: a meta-analysis.

AIM OF THE STUDY: Results of recent published studies on the association between the COX-2 8473T>C polymorphism and the risk of breast cancer have often been conflicting. To make a more precise estimation of the potential relationship, a meta-analysis was performed. MATERIAL AND METHODS: A total of seven case-control studies with 7,033 cases and 9,350 controls were included in the current meta-analysis through searching the databases of PubMed, Embase, and Cochrane Library (up to March 1(st), 2013). The odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the strength of the association. The meta-analysis was conducted in a fixed/random effect model. RESULTS: We found no significant associations for all genetic models after all studies were pooled into the meta-analysis (for C vs. T: OR = 0.974, 95% CI: 0.906-1.047, p = 0.471; for CC vs. TT: OR = 0.957, 95% CI: 0.803-1.140, p = 0.62; for TC vs. TT: OR = 0.964, 95% CI: 0.881-1.055, p = 0.421; for CC + TC vs. TT: OR = 0.963, 95% CI: 0.880-1.053, p = 0.406; for CC vs. TT + TC: OR = 0.978, 95% CI: 0.831-1.15, p = 0.788). We also observed no obvious associations in the subgroup analyses by ethnicity (Caucasian) and source of controls (population based, PB) for all genetic models. CONCLUSIONS: Current evidence suggests that the COX-2 8473T>C polymorphism is not associated with breast cancer risk.

The roles of gut microbiota and its metabolites in diabetic nephropathy.

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, which increases the risk of renal failure and causes a high global disease burden. Due to the lack of sustainable treatment, DN has become the primary cause of end-stage renal disease worldwide. Gut microbiota and its metabolites exert critical regulatory functions in maintaining host health and are associated with many pathogenesis of aging-related chronic diseases. Currently, the theory gut-kidney axis has opened a novel angle to understand the relationship between gut microbiota and multiple kidney diseases. In recent years, accumulating evidence has revealed that the gut microbiota and their metabolites play an essential role in the pathophysiologic processes of DN through the gut-kidney axis. In this review, we summarize the current investigations of gut microbiota and microbial metabolites involvement in the progression of DN, and further discuss the potential gut microbiota-targeted therapeutic approaches for DN.

[A study on the relationship between single nucleotide polymorphisms of interleukin-22 and susceptibility to pulmonary tuberculosis].

OBJECTIVE: To study the association between single nucleotide polymorphisms (SNPs) of interleukin-22 (IL-22) gene and pulmonary tuberculosis. METHODS: From January 2009 to December 2010, clinical data of 479 patients with pulmonary tuberculosis in Shenzhen Third People's Hospital were collected. There were 212 males, and 267 females, aging from 18 to 69 (mean 36 ± 17) years, as well as 358 healthy controls (162 males and 196 females), aging from 18 to 60 (mean 34 ± 13) years. The genotype of SNPs (rs1182844, rs2227473, rs2227476, rs2227480, rs2227485, rs2227508) in IL-22 gene were determined with MassARRAY assay, after Hardy-Weinberg equilibrium test, and the allelic frequency and odds ratio were calculated. Peripheral blood mononuclear cells (PBMCs) from patients with different rs2227473 genotypes were stimulated with anti-CD3 and CD28, and then the IL-22 concentration in supernatant was determined with ELSIA. The SNP allelic frequencies between 2 groups were analyzed by chi-square and IL-22 concentration by t-test. RESULTS: The frequency of allele G of rs2227473 SNP was significantly higher in tuberculosis group than that in the control group (χ(2) = 7.448, P < 0.01, OR = 1.509, 95%CI= 1.121 - 2.030). The other 5 SNPs allele frequency were not statistically significant between the 2 groups (χ(2) = 0.528 - 3.571, all P > 0.05). The secretion of IL-22 was significantly lower in PBMCs with genotype GG of rs2227473 SNP as compared to that in the others (GA/AA) (t = 2.686, P < 0.01). CONCLUSIONS: The results suggested that the rs2227473 SNP in IL-22 was associated with the risk of pulmonary tuberculosis. The allele G was the risk factor of pulmonary tuberculosis. The SNP (rs2227473) may play an important role in the protective immune process against tuberculosis by affecting the IL-22 expression of PBMCs.

A Novel Nomogram Combining Alternative Splicing Events and Clinical Factors for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma.

Due to limitations of sensitive biomarkers, the clinical prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remains poor. Alternative splicing (AS) is the basis of both transcriptome and proteome richness, so more and more evidence indicates an important relationship between AS and tumor progression. The aim of this study was to offer a comprehensive analysis on AS events and then investigate its potentials as a new biomarker for patients with squamous cell carcinoma of the head and neck. In this study, univariate assays were conducted to examine the prognosis-associated AS events, and we screened 4068 survival-related AS events in 2573 genes. Then, the AS events related to survival were further determined and analyzed using LASSO regression and multivariate assays, and an eleven-AS signature was developed. Kaplan-Meier assays indicated patients with high-risk scores exhibited a shorter OS than those with low-risk scores. Multivariate assays further demonstrated that the signature's risk score was independent of HNSCC survivals. Meanwhile, we analyzed the clinical association of AS-based prognostic signature in HNSCC patients and observed that tumor specimens with advanced stages and grades exhibited a high risk score. In addition, the results of survival nomogram revealed that predicted outcomes and actual outcomes were highly consistent. Overall, our group showed an eleven-AS signature of HNSCC, which could be regarded as a separate prognostic factor.

External electric field: a new catalytic strategy for the anti-Markovnikov hydrohydrazination of parent hydrazine.

The anti-Markovnikov hydroamination reaction is considered to be a particular challenge, and one of the reactants, parent hydrazine, is also regarded as a troubling reagent. In this study, we first studied the hydrohydrazination of parent hydrazine via an effective and green catalyst-external electric field (EEF). The calculation results demonstrated that the anti-Markovnikov and Markovnikov pathways are competitive when there was no catalyst. EEF oriented along the negative direction of the X axis (F x ) accelerated the anti-Markovnikov addition reaction. Moreover, it lowered the barrier height of the first step by 16.0 kcal mol-1 (from 27.8 to 11.8 kcal mol-1) when the field strength was 180 (×10-4) au. Under the same conditions, the Markovnikov reaction pathway was inhibited, which means that EEF achieved the specificity of hydrohydrazination. The solvents are favorable for the first step addition reaction, particularly the synergy between solvents and F x lowered the barrier heights by 8.3 (C6H6) and 10.7 (DMSO) kcal mol-1 for an F x = -60 (×10-4) au. Besides, the introduction of the electron-withdrawing substituent (trifluoromethyl) is also a good strategy to catalyze hydrohydrazination, while the electron-donating group (methoxy) is unfavorable.