TGF-ß signaling regulates differentiation of MSCs in bone metabolism: disputes among viewpoints.

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into cells of different lineages to form mesenchymal tissues, which are promising in regard to treatment for bone diseases. Their osteogenic differentiation is under the tight regulation of intrinsic and extrinsic factors. Transforming growth factor ß (TGF-ß) is an essential growth factor in bone metabolism, which regulates the differentiation of MSCs. However, published studies differ in their views on whether TGF-ß signaling regulates the osteogenic differentiation of MSCs positively or negatively. The controversial results have not been summarized systematically and the related explanations are required. Therefore, we reviewed the basics of TGF-ß signaling and summarized how each of three isoforms regulates osteogenic differentiation. Three isoforms of TGF-ß (TGF-ß1/ß2/ß3) play distinct roles in regulating osteogenic differentiation of MSCs. Additionally, other possible sources of conflicts are summarized here. Further understanding of TGF-ß signaling regulation in MSCs may lead to new applications to promote bone regeneration and improve therapies for bone diseases.

Electrochemical biosensor based on the integration of maple leaf-like gold nanocrystal and truncated aptamer for detection of α-amanitin with high sensitivity, selectivity and rapidity.

This study reports the fabrication of three-dimensional gold nanocrystals as sensing material in the presence of l-glutathion and high-performance aptamer with 20 bases of α-amanitin via truncation and optimization of along aptamer. The resulting maple leaf-like gold nanocrystal (ML-Au) exhibits an improved catalytic activity due to more exposed high-index facets. The use of truncated aptamer increases the sensitivity by 15 times and reduces the reaction time by two times compared with those of original aptamer. An α-amanitin electrochemical biosensor constructed by integrating ML-Au nanocrystals with truncated aptamer exhibits high sensitivity, selectivity and rapidity. An increase of the α-amanitin concentration in the range of 1 × 10-14-1 × 10-9 M causes a linear decrease in the amperometric current with a limit of detection of 2.9 × 10-15 M (S/N = 3). The proposed analytical method is satisfactorily used for electrochemical sensing of α-amanitin in urine and wild mushroom samples.

Aerobic CuBr2-Catalyzed Oxidative Coupling Reaction of Amidines with Exocyclic α,ß-Unsaturated Cycloketones for the Synthesis of Spiroimidazolines.

A CuBr2-catalyzed cascade reaction of amidines with exocyclic α,ß-unsaturated cycloketones was developed, affording a large variety of spiroimidazolines in moderate to excellent yields. The reaction process involved the Michael addition and copper(II)-catalyzed aerobic oxidative coupling, in which O2 from air acted as the oxidant and H2O was the sole byproduct.

I2/FeCl3-Catalyzed Domino Reaction of Aurones with Enamino Esters for the Synthesis of Highly Functionalized Pyrroles.

A novel and efficient I2/FeCl3-catalyzed domino reaction of aurones with enamino esters via Michael addition, iodination, intramolecular nucleophilic substitution, and spiro ring opening processes has been developed, affording a vast variety of polysubstituted pyrroles in moderate to excellent yields. This protocol features mild reaction conditions, broad substrate scope, high atom economy and efficiency, and feasibility for large-scale synthesis. A plausible mechanism for the pyrrole synthesis is proposed.

Gut mycobiota dysbiosis in drug-naïve, first-episode schizophrenia.

Bacterial dysbiosis has been demonstrated in patients with schizophrenia (SCH). The aim of the present study was to investigate alterations in mycobiota composition and fungi-bacteria correlation network in drug-naïve, first episode SCH. We recruited 205 SCH patients and 125 healthy controls (HCs), whose gut bacterial and fungal compositions were characterized by 16S and 18S ribosomal RNA gene amplicon sequencing, respectively. Fungal-bacterial relative correlation network analysis was performed using the Spearman's test and distance correlation. We also computed relative networks connectedness, which represents the ratio of significant interactions (edges) and taxa (nodes) in the network. SCH patients showed lower fungal α-diversity compared with that of HCs. Furthermore, we identified 29 differential fungal markers at multiple taxonomies between SCH patients and HCs. SCH patients also showed a significantly lower fungi-to-bacteria α-diversity ratio compared with that of HCs (p = 1.81 × 10-8). In risk prediction models, we observed that combining bacterial and fungal markers achieved higher accuracy than that of bacterial markers alone (AUC = 0.847 vs AUC = 0.739; p = 0.043). Fungal-bacterial correlation network was denser in HCs than in SCH patients and was characterized by a high number of neighbors (p < 0.05). In addition, an increased abundance of Purpureocillium was associated with more severe psychiatric symptoms and poorer cognitive function in SCH patients (p < 0.05). Our study demonstrated a disrupted and weakened fungi-bacteria network in SCH patients, which might be associated with their clinical manifestations. Future research on fungal-bacterial correlation network is warranted to advance our understanding about the role of mycobiota in the etiology of SCH and to explore novel intervention approaches.

Highly sensitive and selective electrochemical aptasensor with gold-aspartic acid, glycine acid-functionalized and boron-doped graphene quantum dot nanohybrid for detection of α-amanitin in blood.

Poisonous mushroom may cause fatal harm to human and animal, but its rapid detection still faces a great challenge. The paper reports synthesis of gold-aspartic acid, glycine acid-functionalized and boron-doped graphene quantum dot nanohybrid (AGB-GQD@Au) for the electrochemical detection of α-amanitin. AGB-GQD was prepared by pyrolysis and then reacted with chloroauric acid to produce gold nanoparticles. AGB-GQD@Au offers 12.5 nm-sized particles and Schottky heterojunction, improving the catalytic activity. AGB-GQD@Au connected with hairpin DNA and thionine by Au-S bonds was used as redox probe for electrochemical detection of α-amanitin coupled with one target-induced DNA cycle amplification strategy. α-Amanitin specifically hybridizes with aptamer in duplex DNA to release auxiliary strand DNA. The released DNA triggers one DNA cycle process and brings one redox probe to the electrode surface. By the DNA cycle, one target brings many redox probes to the electrode surface, producing a significant signal amplification. The detection signal was further enhanced by the catalysis of AGB-GQD@Au towards redox of thionine. Differential pulse voltammetric current increases linearly with the increasing α-amanitin in the range from 4 to 4 × 105 fM with the detection limit of 1.2 fΜ (S/N = 3). The analytical method provides advantages of sensitivity, selectivity and repeatability. It has been successfully applied in electrochemical detection of α-amanitin in blood.

A synergistic effect between family intervention and rTMS improves cognitive and negative symptoms in schizophrenia: A randomized controlled trial.

OBJECTIVE: The present study explored an efficient new therapy that combined repetitive transcranial magnetic stimulation (rTMS) and family intervention in addition to risperidone to improve schizophrenia. METHODS: A randomized controlled trial (January 2016-September 2017) involving 200 patients, of which 188 patients completed the 12-week study, and 50 controls were conducted in the research. The patients were randomly assigned to 12 weeks of treatment with risperidone alone (risperidone group), rTMS and risperidone (rTMS group), family intervention and risperidone (family intervention group), rTMS and risperidone plus family intervention (combined group). MATRICS Consensus Cognitive Battery (MCCB) and the Positive and Negative Symptoms Scale (PANSS) were used to evaluate treatment efficacy. Repeated measures analysis of variance (RMANOVA) were performed to evaluate different treatment efficacy between four groups after 12 weeks of treatment. RESULTS: (1) There were no significant differences in sex, age, education, cognitive function, or PANSS scores between the four groups at baseline (p's > 0.05). (2) There was a significant decrease in the PANSS scores and an increase in the MCCB scores after 12 weeks of treatment in all groups (time effect p's < 0.001). (3) The improvements in positive symptoms and negative symptoms were more obvious in the combined group than in other groups (p's < 0.05). (4) The combined group showed the superior effect in cognition function after 12 weeks. (5) And, interestingly, a remarkable synergistic effect between rTMS and family intervention therapy was observed. CONCLUSION: There was a synergistic effect between rTMS and the family intervention as an effective combined therapy in improving schizophrenia. This study is registered with Chictr.org, number ChiCTR1900024422 (http://www.chictr.org.cn/edit.aspx?pid=34285&htm=4).

[Correlation between serum levels of homocysteine and folate and cognitive dysfunction in first-episode schizophrenics].

OBJECTIVE: To explore the correlation between serum levels of homocysteine (Hcy) and folate and cognitive function in first-episode drug-naїve schizophrenics. METHODS: A total of 60 first-episode schizophrenics (schizophrenia group) from our hospital and 60 healthy individuals (control group) were enrolled.Serum levels of folate and Hcy were measured with electrochemical luminescence method and enzymatic cycling assay respectively. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate the cognitive function. RESULTS: Serum level of folate in schizophrenia group (4.1 ± 1.9 ng/ml) was lower than that in control group (7.5 ± 1.9 ng/ml) (P < 0.001). And serum level of Hcy in schizophrenia group (27 ± 9 µmol/L) was significantly higher than that in control group (18 ± 6 µmol/L) (P = 0.006). Serum level of folate in schizophrenia group had negative correlations with Hcy level (r = -0.38, P = 0.002) and negative symptoms (r = -0.25, P < 0.05) while Hcy level was negatively correlated with cognitive function scores (r = -0.38, r = -0.33, r = -0.30, r = -0.30, P < 0.05). CONCLUSION: Serum level of folate decreases while serum level of Hcy increases in first-episode schizophrenics. Both have some relevance with mental symptom and cognitive dysfunction.

[Association of serum folic acid and homocysteine levels and 5, 10-methylenetetrahydrofolate reductase gene polymorphism with schizophrenia].

OBJECTIVE: To explore the association between serum concentrations of folic acid and homocysteine (HCY), 5, 10-methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and schizophrenia. METHODS: A total of 130 schizophrenics (schizophrenia group) from our hospital and 80 healthy individuals (control group) were enrolled. The serum concentration of homocysteine was measured by the electrochemical luminescence method, the concentration of serum folic acid by enzymatic cycling assay and MTHFR C667T genotype by PCR-DNA microarray. And positive and negative syndrome scale (PANSS) was used to evaluate the mental symptoms. RESULTS: (1) Serum HCY level in schizophrenia group was higher than that in control group [(20 ± 10) vs (11 ± 3) µmol/L; P < 0.001] while serum folate level in schizophrenia group was lower than that in control group [(6 ± 4) vs (9 ± 3) ng/ml; P < 0.001]; (2) the frequencies of CC, CT and TT in MTHFR C677T alleles were 13.1%, 50.0% and 36.9% in schizophrenia group versus 30.0%, 47.5% and 22.5% in control group respectively. Statistical significant inter-group difference existed in the frequencies of genotypes (χ² = 36.806, P < 0.05) . The frequencies of T and C alleles were 61.9%, 38.1% in schizophrenia group versus 46.25%, 53.75% in control group respectively. Statistical significant inter-group difference existed in the frequency of T allele (χ² = 9.872, P < 0.05). The frequency of TT genotype in schizophrenia group was 61.9% versus 22.5% in control group. Statistically significant inter-group difference existed in the frequency of TT homozygous mutation (χ² = 4.780, P < 0.05); (3) correlation analysis showed that serum folate level in schizophrenia group had a negative correlation with HCY level (r = -0.418, P < 0.001) . Serum HCY level had a positive correlation with negative symptoms scores (r = 0.345, P < 0.001) and serum folate level was negatively correlated with negative symptoms scores (r = -0.386, P < 0.001); (4) the serum HCY level in schizophrenia group with TT genotype was significantly higher than those with CC and CT genotypes (P < 0.05). CONCLUSION: There is a certain correlation between the serum levels of folate and HCY and the symptoms of schizophrenia. And MTHFR C677T polymorphism is a possible risk factor for schizophrenia.