A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3.

The X-linked GRIA3 gene encodes the GLUA3 subunit of AMPA-type glutamate receptors. Pathogenic variants in this gene were previously reported in neurodevelopmental diseases, mostly in male patients but rarely in females. Here we report a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) identified in a 1-year-old female patient with severe epilepsy and global developmental delay. When exogenously expressed in human embryonic kidney (HEK) cells, GLUA3_R660T showed slower desensitization and deactivation kinetics compared to wildtype (wt) GLUA3 receptors. Substantial non-desensitized currents were observed with the mutant but not for wt GLUA3 with prolonged exposure to glutamate. When co-expressed with GLUA2, the decay kinetics were similarly slowed in GLUA2/A3_R660T with non-desensitized steady state currents. In cultured cerebellar granule neurons, miniature excitatory postsynaptic currents (mEPSCs) were significantly slower in R660T transfected cells than those expressing wt GLUA3. When overexpressed in hippocampal CA1 neurons by in utero electroporation, the evoked EPSCs and mEPSCs were slower in neurons expressing R660T mutant compared to those expressing wt GLUA3. Therefore our study provides functional evidence that a gain of function (GoF) variant in GRIA3 may cause epileptic encephalopathy and global developmental delay in a female subject by enhancing synaptic transmission.

Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory.

N-methyl-D-aspartic acid type glutamate receptors (NMDARs) play critical roles in synaptic transmission and plasticity, the dysregulation of which leads to cognitive defects. Here, we identified a rare variant in the NMDAR subunit GluN2A (K879R) in a patient with intellectual disability. The K879R mutation enhanced receptor expression on the cell surface by disrupting a KKK motif that we demonstrated to be an endoplasmic reticulum retention signal. Expression of GluN2A_K879R in mouse hippocampal CA1 neurons enhanced the excitatory postsynaptic currents mediated by GluN2A-NMDAR but suppressed those mediated by GluN2B-NMDAR and the AMPA receptor. GluN2A_K879R knock-in mice showed similar defects in synaptic transmission and exhibited impaired learning and memory. Furthermore, both LTP and LTD were severely impaired in the KI mice, likely explaining their learning and memory defects. Therefore, our study reveals a new mechanism by which elevated synaptic GluN2A-NMDAR impairs long-term synaptic plasticity as well as learning and memory.

Prenatal Exposure to Legacy and Alternative Per- and Polyfluoroalkyl Substances and Neuropsychological Development Trajectories over the First 3 Years of Life.

The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother-child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal-social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.

Fetal Glucocorticoid Mediates the Association between Prenatal Per- and Polyfluoroalkyl Substance Exposure and Neonatal Growth Index: Evidence from a Birth Cohort Study.

Glucocorticoid plays a key role in the growth and organ maturation of fetus. However, the effect of glucocorticoid on the association between per- and polyfluoroalkyl substance (PFAS) exposure and fetal growth is still unknown. We detected cord cortisol (active glucocorticoid in human) and 34 PFAS concentrations in the maternal serum samples, which were collected from 202 mother-fetus pairs in the Maoming Birth Cohort from 2015 to 2018. The mediation effect of cord cortisol on the association between maternal PFAS and the neonatal growth index (NGI) was estimated. We found that higher PFAS concentrations were associated with lower NGI in terms of ponderal index, birth weight (BW), head circumference (HC), and its z-scores (BWZ and HCZ) (P < 0.05). Fetal cortisol could mediate 12.6-27.3% of the associations between PFAS and NGI. Specifically, cord cortisol mediated the association between branched perfluorooctane sulfonate (branched PFOS) and HCZ by 20.4% and between perfluorooctanoate (PFOA) and HCZ by 27.3%. Our findings provide the first epidemiological data evincing that fetal cortisol could mediate the association between prenatal PFAS exposure and fetal growth. Further investigations are recommended to elucidate the interactions among cord cortisol, PFAS, and fetal growth.

Adult Kerion Celsi Caused by Trichophyton tonsurans Secondary to Black Dot Tinea Capitis.

A 34-year-old female patient presented with hair loss due to black dot tinea capitis caused by Trichophyton tonsurans for 6 months. Hair loss progressed to painful swelling for 2 months due to kerion Celsi which may be associated with treatment like topical minoxidil, antibiotic and corticosteroid previously. The patient was treated with oral Itraconazole initially without success but cured by Terbinafine eventually. It's very interesting that the patient caught kerion celsi secondary to a four-month history of hair loss due to black dot tinea capitis.

[Association of Serine/Threonine Phosphoprotein Phosphatase 4C Expression With Prognosis of Gastric Cancer].

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.

Chlorinated Polyfluorinated Ether Sulfonates and Thyroid Hormone Levels in Adults: Isomers of C8 Health Project in China.

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

[Formation and development of "Xiang thinking" in traditional Chinese medicine].

"Xiang thinking" is the main thinking mode in traditional Chinese medicine(TCM) with both philosophical and scientific connotations, and has an important influence on the emergence and development of TCM. This study systematically expounded the philosophical connotation and characteristics of "Xiang thinking", and its application in the construction of TCM theory, clinical syndrome differentiation and treatment, the formation of medicinal properties, and interpretation of efficacy of Chinese medicine. "Xiang thinking" in TCM develops and changes continuously with practical application, and its historical evolution can be summarized into three stages, i.e., "Ying Xiang(corresponding to Xiang)" "Fa Xiang(following Xiang)", and "Bian Xiang(differentiating Xiang)". The understanding of Xiang is based on the means and methods of human observation of things and the backgrounds of the philosophy, science, and development. The result of comparison depends on the depth and breadth of Xiang. In the real world, Xiang is showing new construction characteristics with multiple dimensions and levels. Therefore, this study proposed the thinking of "Bian Xiang", which is expected to provide a thinking approach that can realize the transformation from "Xiang thinking" to scientific research for the exploration and innovative research on life origin in the field of contemporary and TCM.

[Metabolites of endophytic fungus Nigrospora sphaerica S5 from Myoporum bontioides].

The endophytic fungus Nigrospora sphaerica S5 derived from the semi-mangrove plant Myoporum bontioides was fermented. Its metabolites were purified by column chromatography. Nine compounds were obtained and identified as terezine P(1), 3-(1-hydroxyethyl)-4-methyl dihydrofuran-2(3H)-one(2), methylhydroheptelidate(3), hydroheptelidic acid(4), 5, 7-dimethoxy-4, 6-dimethylphthalide(5),(3R,4S)-(-)-4-hydroxymellein(6), pestalopyrone(7), indole-3-formaldehyde(8) and p-hydroxybenzaldehyde(9) by spectroscopic techniques. Terezine P(1) was a new alkaloid belonging to the terezine class with a pyrazine ring. Compounds 2-7 were lactones, of which 3 and 4 belonged to sesquiterpenes. Compounds 8 and 9 were indole alkaloids and phenols, respectively. Compounds 3-6 were purified from Nigrospora sp. for the first time. These compounds showed different degrees of antibacterial activity against Staphylococcus aureus, Escherichia coli of O6 serotype and E. coli of O78 serotype.

[Effect of granules made by new-medicinal parts of Crocus sativus on hyperuricemia in rats and its mechanism].

To explore the effect of the granules made by new-medicinal parts of Crocus sativus(NMPCS) on hyperuricemia(HUA) in rats, the rat model of HUA was established by intramuscular injection of 3% potassium oxonate and intraperitoneal injection of 4% pyrazinamide. The content of serum uric acid was monitored every week for 3 consecutive weeks. After the experiment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen(BUN), and xanthine oxidase(XOD) were determined. The protein and gene expressions of XOD were determined by Western blot method and fluorescence quantitative polymerase chain reaction(qPCR), and the morphological changes in the liver tissue were performed by hematoxylin-eosin(HE) staining. The results showed that as compared with the model group, the levels of serum uric acid in the positive drug group and the low, medium, and high-dose NMPCS groups were lower(P<0.05), the levels of urine uric acid in the high-dose NMPCS group were decreased(P<0.01), and there was no statistical difference in the medium and low-dose NMPCS groups. The levels of BUN in the high and low-dose NMPCS groups were decreased(P<0.05), and the levels of serum creatinine did not change in the administration groups. The positive drug group and the low, medium, and high-dose NMPCS groups significantly reduced the liver damage, with only a few hepatocytes vacuolization and a small number of red blood cells in the central venous area. The nephridial tissue structure was slightly abnormal, with a small number of red blood cell infiltration, and no obvious inflammatory cell infiltration was found in the glomerulus in these groups. No degeneration was found in renal tubular epithelial cells, with mild glomerular and tubular lesions and a small amount of sodium urate deposition and crystallization in the positive drug group and the low, medium, and high-dose NMPCS groups. The relative protein expressions of XOD in the positive drug group and the high dose NMPCS group were decreased(P<0.05), and the relative mRNA expressions of XOD in the positive drug group and the high and low-dose NMPCS groups were decreased as well(P<0.05). The above results show that NMPCS reduces uric acid in rats with HUA by regulating XOD, which provides a certain experimental basis for the development of NMPCS as a new medicine for the treatment of HUA.

The protective effort of GPCR kinase 2-interacting protein-1 in neurons via promoting Beclin1-Parkin induced mitophagy at the early stage of spinal cord ischemia-reperfusion injury.

In spinal cord ischemia-reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2-interacting protein-1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia-reperfusion. However, the overexpression of adeno-associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin-1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN-induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia-reperfusion injury and, hence, might serve as a new research site for the protection of ischemia-reperfusion injury.

Associations between serum isomers of perfluoroalkyl acids and metabolic syndrome in adults: Isomers of C8 Health Project in China.

BACKGROUND: Exposure to perfluoroalkyl acids (PFAAs) is known to be associated with metabolic disorders. However, whether PFAAs isomers are associated with metabolic syndrome (MetS) still remains unknown. OBJECTIVES: To explore the associations between serum PFAAs isomers and MetS. METHODS: We recruited 1,501 adults from a cross-sectional study, the "Isomers of C8 Health Project in China" to investigate the associations between PFAAs isomers and MetS. A total of 20 PFAAs including the isomers of PFOS and PFOA were detected. Logistic regression models and restricted cubic spline models were used to evaluate the relationship of serum PFAAs isomers exposure with MetS and its components as well after adjusting for covariates. RESULTS: The MetS prevalence in our study was 43.0%. The serum levels of both PFOS and PFOA isomers were higher in participants with MetS than that with non-MetS (p < 0.05). We found positive associations for per natural log-transformed ng/mL of branched perfluorooctane sulfonate (br-PFOS) (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.01, 1.38)) linear perfluoronanoic acid (n-PFOA) (OR = 1.35, 95% CI: 1.16, 1.58) and perfluoro-6-methylpheptanoic acid (6 m-PFOA) (OR = 1.32, 95% CI: 1.11, 1.57) with higher odds of MetS after covariates adjustment, while null association was observed for linear isomers of PFOS (OR = 1.09, 95% CI: 0.94, 1.25). We found a nonlinear dose-response relationship with a "threshold" effect in serum br-PFOS isomers with MetS, in which the odds of MetS increased quickly with increasing serum br-PFOS isomers under low exposure (p for nonlinearity = 0.030). CONCLUSION: We report new evidence of associations between PFAAs isomers and MetS and the nonlinearity of dose-response relationship with br-PFOS isomers. Our findings indicate that more attention is needed to pay on the nonlinearity of dose-response relationship when investigate the association of PFAAs isomers with human health.

Complex microbial communities inhabiting natural Cordyceps militaris and the habitat soil and their predicted functions.

Cordyceps militaris is a traditional Chinese medicinal food that is challenging to quality maintaining while mass cultivation. Many studies have found that abundant microbes inhabit Ophiocordyceps sinensis and perform important functions for their host. In this study, our objective was to reveal the microbial communities that inhabit C. militaris and analyze their potential functions. High-throughput sequencing of 16S rRNA and ITS genes was used to compare the diversity and composition of the bacterial and fungal communities associated with naturally occurring C. militaris collected from Yunnan Province, southwestern China. The diversity and richness of the microbial communities and the number of function genes of the bacteria were significantly higher in the habitat soil than in the fruiting body. The sclerotia and stromata samples shared the same microbiota and functions. The main bacterial phyla were Proteobacteria, Acidobacteria, Bacteroidetes and Actinobacteria, and Ascomycota was the main fungal phylum. The growth-promoting bacteria Herbaspirillum and the plant probiotic Phyllobacterium, which may enhance C. militaris quality and facilitate its cultivation, were detected in the fruiting body samples. Genes related to metabolism were more abundant in the soil bacteria, while membrane transport genes were more abundant in the endophytic bacteria of C. militaris. Our study is the first to reveal the unexpectedly high diversity of the microbial communities and the bacterial functions inhabiting the natural C. militaris using high-throughput sequencing, and our results provide insights into mining the functions of microorganisms in the development and quality of C. militaris.

Pseudorivibacter rhizosphaerae gen. nov., sp. nov., isolated from rhizosphere soil of Camellia sinensis (L.) O. Ktze and emended description of the genus Rivibacter.

A Gram-stain-negative, facultative anaerobic, motile and straight rod-shaped bacterium, designated strain C1-9T, was isolated from rhizosphere soil of Camellia sinensis (L.) O. Ktze collected from a tea garden in Huize, south-western PR China. Cells were oxidase-positive and catalase-negative. Growth occurred at 20-40 °C and pH 6.0-10.0, with an optimal growth at 30 °C and pH 7.0. The respiratory quinone was detected as ubiquinone-8 (Q-8). The major fatty acids were identified as summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and summed feature 8 (C18 : 1ω7c or C18 : 1ω6c). The cellular polar lipids contained phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids, two unidentified lipids, one unidentified aminophospholipid and one unidentified aminolipid. The polyamine types were detected as 1,8-diaminooctane and 2-hydroxyputrescine. The genomic DNA G+C content was 68.6 mol%. Based on the results of 16S rRNA gene sequence analysis, strain C1-9T (MF687442) showed highest sequence similarity to Rivibacter subsaxonicus DSM 19570T (97.1 %). The phylogenetic tree based on 16S rRNA gene sequences showed that strain C1-9T clustered close to R. subsaxonicus DSM 19570T, Methylibium petroleiphilum CCTCC AB 2014193T and species belonging to the genera Rhizobacter and Piscinibacter. The phylogenomic tree indicated that strain C1-9T formed a clade with R. subsaxonicus. The average nucleotide identity value was 76.0 % between strain C1-9T and R. subsaxonicus DSM 19570T, which is lower than the prokaryotic species delineation threshold of 95.0-96.0 %. The polyphasic taxonomic characteristics indicated that strain C1-9T represents a novel species of a new genus within the order Burkholderiales, for which the name Pseudorivibacter rhizosphaerae gen. nov., sp. nov. (type strain C1-9T = KCTC 62325T=CGMCC 1.13864T) is proposed.

Biological Activities of Two Essential Oils from Pogostemon cablin and Eupatorium fortunei and Their Major Components against Fungi Isolated from Panax notoginseng.

Panax notoginseng (Burkill) F.H.Chen (Araliaceae), of which the dry root and rhizome are precious traditional Chinese medicine, suffers severely from diseases during planting. Essential oils (EOs) with antimicrobial activity are a possibility for the development of green pesticides. We extracted EOs from Pogostemon cablin (Blanco) Benth. and Eupatorium fortunei Turcz., respectively and tested their inhibitory rates on fungi isolated from diseased P. notoginseng by the Oxford cup method. The compounds of the EO were identified by GC/MS and the minimum inhibitory concentrations (MICs) of the EOs and their main components were evaluated by the 96-well plate method. We also mixed P. cablin EO, E. fortunei EO and hymexazol in pairs to explore whether their combinations produce stronger antifungal effects than individual components. Finally, we evaluated the effects of the EOs against Fusarium oxysporum in vivo. P. cablin EO and E. fortunei EO exhibited different antifungal activities against fungi, with the inhibitory rates of 21.02 %-100 % and 54.84 %-100 % and MICs of 0.07-0.88 mg/mL and 0.20-1.17 mg/mL, respectively. Pogostone (24.96 %) and thymol (15.64 %) were the major compounds of P. cablin EO and E. fortunei EO, respectively, and they exhibited stronger antifungal activities than EOs, with MICs of 0.008-0.078 mg/mL and 0.12-0.31 mg/mL, respectively. Moreover, hymexazol was mixed with E. fortunei EO, and the inhibitory effect against Cylindrocarpon destructans was enhanced with a synergistic effect. The disease incidence and disease index of EO treatments decreased significantly in vivo. Based on our study, P. cablin EO and E. fortunei EO have great potential to be developed into green fungicides for use in agriculture to control diseases of P. notoginseng.

Mixtures of fluopyram and abamectin for management of Meloidogyne incognita in tomato.

The southern root-knot nematode (RKN), Meloidogyne incognita, causes significant damage to vegetable production and is a major problem in greenhouse tomatoes. The effect of a combination of fluopyram and abamectin, at a mass ratio of 1:5, was studied for RKN control. Pot trials showed that fluopyram, abamectin, and their combination at three dosages increased the height, stem diameter, root fresh weight, shoot fresh weight, and the root length of tomato plants. The RKN control efficacy of the 1:5 combination at 450 g a.i./ha was 74.06% at 30 days after transplanting (DAT), and the control efficacy of the combination at 337.5 and 450 g a.i./ha differed significantly from those of other treatments at 60 DAT. The root-galling index (RGI) control efficacy of the combination at 450 g a.i./ha and of fluopyram (41.7% SC) only at 450 g a.i./ha were better than the control efficacies of other treatments, and these two treatments significantly increased root activity. Field trial results showed that the soil nematode control efficacy was similar to that of the pot trials at 30 and 60 DAT. The RGI control efficacy of the combination at 337.5 and 450 g a.i./ha and of fluopyram (41.7% SC) only at 450 g a.i./ha differed significantly from those of the two other treatments. The tomato yields of the 1:5 combination at 450 g a.i./ha were increased by 24.07 and 23.22% compared to the control in field trials during two successive years. The combination of fluopyram and abamectin provides good nematode measure, and it can increase tomato yields. It provides an effective solution for the integrated management of southern RKN.

Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK.

Obesity is a serious health challenge in the world, and searching effective drugs to cure obesity is of great importance. 1-Deoxynojirimycin (DNJ) is extracted from mulberry leaves and acts as an α-glucosidase inhibitor to lower blood glucose. Recent studies demonstrated that it also has anti-obesity effect, but the mechanisms remain unknown. In our present study, we mainly examined the effects of DNJ on beige remodeling of 3T3-L1 preadipocytes. We observed that DNJ didn't affect the mRNA levels of fatty acid binding protein 4 (aP2), peroxisome proliferator-activated receptor γ (PPARγ), preadipocyte factor-1 (Pref-1) as well as the mitochondrial uncoupling protein 1 (UCP1), PR domain containing protein 16 (PRDM16), transmembrane protein 26 (TMEM26) in undifferentiated preadipocytes. But after inducing 3T3-L1 preadipocytes to differentiation with white or beige adipogenic medium, DNJ significantly reduced aP2, PPARγ and Pref-1 expressions, while up-regulated the expressions of UCP1, PRDM16 and TMEM26, accompanying with decreased lipid deposition. The ratio of p-AMPK/AMPK was up-regulated by DNJ (10 µM) treatment for 10 days, and the effects of DNJ on p-AMPK/AMPK, UCP1 and PRDM16 could be blocked by AMPK inhibitor Compound C. These results demonstrated that hypoglycemic agent DNJ could suppress the adipogenesis during the differentiation of white preadipocytes, and promote the switch of white preadipocytes to beige adipocytes via activating AMPK, which provided new mechanisms for explaining the benefits of DNJ on obesity-related disorders.

Dyella tabacisoli sp. nov., a bacterium isolated from an arable soil sample of Nicotiana tabacum L.

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated strain L4-6T, was isolated from an arable soil sample of tobacco in Huize, south-western China and subjected to polyphasic taxonomic characterization. The cells showed oxidase-positive and catalase-positive reactions. Growth occurred at 20-35 °C, at pH 5.0-8.0 and with 0-2 % (w/v) NaCl, optimally at 30 °C, pH 6.0-7.0 and 0-1 % (w/v) NaCl. The major respiratory lipoquinone was ubiquinone-8. The predominant cellular fatty acids (>10.0 %) were identified as summed feature 9 (iso-C17 : 1ω9c or C16 : 0 10-methyl), iso-C15 : 0 and iso-C17 : 0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, two unidentified aminophospholipids and five unidentified aminolipids. The genomic DNA G+C content was 60.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain L4-6T should be affiliated to the genus Dyella and formed a clade with the most closely related organism Dyella soli JS12-10T. 16S rRNA gene sequences similarity analysis showed that strain L4-6T was mostly closely related to D. soli JS12-10T (98.73 %) and Dyella lipolytica DHOB07T (98.02 %). DNA-DNA hybridization data indicated that strain L4-6T represented a novel genomic species belonging to the genus Dyella. The polyphasic taxonomic characteristics indicated that the strain L4-6T represents a novel species of the genus Dyella, for which the name Dyellatabacisoli sp. nov. (type strain L4-6T=CGMCC 1.16273T=KCTC 62035T) is proposed.

Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China.

Exposure to chemicals may affect liver enzyme to increase the risk of liver diseases. Perfluoroalkyl acids (PFAAs) are one kind of persistent organic pollutants with hepatotoxic effect in organism. However, data is scarce to characterize the hepatotoxic effects of specific structural PFAA isomers in general population. To address this data gap, we evaluated the association between serum PFAAs concentration and liver function biomarkers in the Isomers of C8 Health Project in China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure 18 serum PFAAs, except for linear and branched isomers of PFOA/PFOS, nine perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) were also included, in 1605 adult residents of Shenyang, China. Values for nine serum liver function biomarkers were determined by full-automatic blood biochemical analyzer. Linear regression was used to evaluate associations between PFAAs and continuous liver function biomarkers and logistic regression to assess markers dichotomized per clinical reference intervals. Results indicated that serum PFAAs concentrations were associated with liver biomarker levels suggestive of hepatotoxicity, especially for liver cell injury. For example, a 1 ln-unit increase in total- perfluorooctanoic acid (PFOA) exposure was associated with a 7.4% [95% confidence interval (CI): 3.9%, 11.0%] higher alanine aminotransferase (ALT) level in serum. Interestingly, we observed association between branched PFAA isomers and liver biomarkers. For example, one ln-unit increase in branched perfluorooctane sulfonate (PFOS) isomers exposure was associated with a 4.3% increase in ALT level (95% CI: 1.2%, 7.4%) and a 33.0% increased odds of having abnormal ALT (95% CI: 5.0%, 67.0%). Also, we found that PFNA had positive association with ALT [(6.2%, 95% CI: 3.1%, 9.4%) and AST levels (2.5%, 95% CI: 0.5%, 4.5%)]. Logistic regression results showed that PFPeA, PFHxA, PFNA, PFDoDA, PFTrDA and PFTeDA had statistically association with abnormal prealbumin. Conclusively, our results support previous studies showing association between PFAAs exposure and liver function biomarkers. We found new evidence that branched PFAAs isomer exposure is associated with the risk of clinically relevant hepatocellular dysfunction.