Cobalt's Dual Role in Promoting C3-Glycosylation of Indoles: Unraveling Mechanistic Insights.

In this study, we present a cobalt-catalyzed C3-glycosylation of indoles using unfunctionalized glycals, yielding 3-indolyl-C-deoxyglycosides. These compounds hold promise as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for treating type 2 diabetes. Control experiments unveiled that cobalt assumes a dual role, facilitating catalytic C-glycosylation while unexpectedly driving the anomerization of α-anomers through endocyclic cleavage of the C1-O5 bond, resulting in the formation of ß-C-deoxyglycosides. Furthermore, density functional theory (DFT) calculations shed light on the reaction mechanism, emphasizing the significant role of the pyridine group of indole in stabilizing transition states and intermediates.

Universality and scaling in complex networks from periods of Chinese history.

Critical physical systems with large numbers of molecules can show universal and scaling behaviors. It is of interest to know whether human societies with large numbers of people can show the same behaviors. Here, we use network theory to analyze Chinese history in periods 209 BCE-23 CE and 515-618 CE) related to the Western Han-Xin Dynasty and the late Northern Wei-Sui Dynasty, respectively. Two persons are connected when they appear in the same historical event. We find that the historical networks from two periods separated about 500 years have interesting universal and scaling behaviors, and they are small-world networks; their average cluster coefficients as a function of degree are similar to the network of movie stars. In the historical networks, the persons with larger degrees prefer to connect with persons with a small degree; however, in the network of movie stars, the persons with larger degrees prefer to connect with persons with large degrees. We also find an interesting similar mechanism for the decline or collapse of historical Chinese dynasties. The collapses of the Xin dynasty (9-23 CE) and the Sui dynasty (581-618 CE) were initiated from their arrogant attitude toward neighboring states.

Diagnosis, treatment and genetic analysis of a case of Alstrom syndrome caused by compoud heterozygous mutation of ALMS1.

Alstrom syndrome is a rare autosomal recessive disorder disease caused by mutations in the ALMS1 gene, and its typical clinical manifestations include cone-rod retinal dystrophy, sensorineural deafness, obesity, insulin resistance, diabetes mellitus, hypertriglyceridemia, non-alcoholic fatty liver, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. In this report, we followed up a young male patient presenting with diabetes mellitus, who was later diagnosed with blindness, deafness, hyperlipidemia, obesity, fatty liver, and insulin resistance. Genetic testing revealed a compound heterozygous mutation in ALMS1 from the patient, with an exon 8 c.5535delG (p.S1847Lfs*24) mutation inherited from the maternal side and an exon 16 c.10819C>T (p.R3607X) mutation from the paternal side. Neither of these two mutations had been previously recorded in the known ALMS1 genetic mutation database. Hyperinsulinemic-euglycemic clamp test indicated that the insulin sensitivity index was significantly improved in the patient after taking oral dapagliflozin. By summarizing and analyzing this case, we should consider Alstrom syndrome in clinical adolescent-onset diabetes patients with blindness, deafness, severe insulin resistance, and lipid metabolism disorder. These two new mutation sites identified in this case enrich the genetic mutation database of the ALMS1 gene, and the follow-up data of this study provide new evidence for deciding appropriate glucose-lowering regimens in patients with Alstrom syndrome.

Heterogeneity of neuronal properties determines the collective behavior of the neurons in the suprachiasmatic nucleus.

Circadian rhythms have been observed in behavioral and physiological activities of living things exposed to the natural 24 h light-darkness cycle. Interestingly, even under constant darkness, living organisms maintain a robust endogenous circadian rhythm suggesting the existence of an endogenous clock. In mammals, the endogenous clock is located in the suprachiasmatic nucleus (SCN) which is composed of about 20,000 neuronal oscillators. These neuronal oscillators are heterogeneous in their properties, including the intrinsic period, intrinsic amplitude, light information sensitivity, cellular coupling strength, intrinsic amplitudes and the topological links. In this review, we introduce the influence of the heterogeneity of these properties on the two main functions of the SCN, i.e. the free running rhythm in constant darkness and entrainment to the external cycle, based on mathematical models where heterogeneous neuronal oscillators are coupled to form a network. Our findings show that the heterogeneities can alter the free running periods under constant darkness and the entrainment ability to the external cycle for the SCN by controlling a fine balance between flexibility and robustness of the clock. These findings can explain experimental observation, e.g., why the free running periods and entrainment abilities are different between species, and shed light on the heterogeneity of the SCN network.

Spraying Brassinolide improves Sigma Broad tolerance in foxtail millet (Setaria italica L.) through modulation of antioxidant activity and photosynthetic capacity.

To explore the role of Brassinolide (BR) in improving the tolerance of Sigma Broad in foxtail millet (Setaria italica L.), effects of 0.1 mg/L of BR foliar application 24 h before 3.37 g/ha of Sigma Broad treatment at five-leaf stage of foxtail millet on growth parameters, antioxidant enzymes, malondialdehyde (MDA), chlorophyll, net photosynthetic rate (P N), chlorophyll fluorescence and P700 parameters were studied 7 and 15 d after herbicide treatment, respectively. Results showed that Sigma Broad significantly decreased plant height, activities of superoxide dismutase (SOD), chlorophyll content, P N, PS II effective quantum yield (Y (II)), PS II electron transport rate (ETR (II)), photochemical quantum yield of PSI(Y (I)) and PS I electron transport rate ETR (I), but significantly increased MDA. Compared to herbicide treatment, BR dramatically increased plant height, activities of SOD, Y (II), ETR (II), Y (I) and ETR (I). This study showed BR pretreatment could improve the tolerance of Sigma Broad in foxtail millet through improving the activity of antioxidant enzymes, keeping electron transport smooth, and enhancing actual photochemical efficiency of PS II and PSI.

Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection.

Vaccination strategies for Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA) infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC), which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113-136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d) crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209-232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine.

A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis.

OBJECTIVE: Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. DESIGN: Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. RESULTS: Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis.

Identification of the immunodominant regions of Staphylococcus aureus fibronectin-binding protein A.

Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a diverse spectrum of human diseases and a leading cause of nosocomial and community-acquired infections. Development of a vaccine against this pathogen is an important goal. The fibronectin binding protein A (FnBPA) of S. aureus is one of multifunctional 'microbial surface components recognizing adhesive matrix molecules' (MSCRAMMs). It is one of the most important adhesin molecules involved in the initial adhesion steps of S. aureus infection. It has been studied as potential vaccine candidates. However, FnBPA is a high-molecular-weight protein of 106 kDa and difficulties in achieving its high-level expression in vitro limit its vaccine application in S. aureus infection diseases control. Therefore, mapping the immunodominant regions of FnBPA is important for developing polyvalent subunit fusion vaccines against S. aureus infections. In the present study, we cloned and expressed the N-terminal and C-terminal of FnBPA. We evaluated the immunogenicity of the two sections of FnBPA and the protective efficacy of the two truncated fragments vaccines in a murine model of systemic S. aureus infection. The results showed recombinant truncated fragment F130-500 had a strong immunogenicity property and survival rates significantly increased in the group of mice immunized with F130-500 than the control group. We futher identified the immunodominant regions of FnBPA. The mouse antisera reactions suggest that the region covering residues 110 to 263 (F1B110-263) is highly immunogenic and is the immunodominant regions of FnBPA. Moreover, vaccination with F1B110-263 can generate partial protection against lethal challenge with two different S. aureus strains and reduced bacterial burdens against non-lethal challenge as well as that immunization with F130-500. This information will be important for further developing anti- S. aureus polyvalent subunit fusion vaccines.

Diagnostic value of HE4 for ovarian cancer: a meta-analysis.

BACKGROUND: Ovarian cancer (OC) is the second most common gynecological cancer and the first cause of death from gynecological malignancy in Western Europe and the USA. While human epididymis-specific protein 4 (HE4) has been reported as a predictive diagnostic index, it has not been widely accepted because of inconsistent conclusions. The aim of this study was to evaluate the diagnostic value of HE4 systematically for ovarian cancer. METHODS: All relevant original studies about HE4 in the diagnosis of ovarian cancer published from January 1974 to May 2011 were retrieved. By measuring methodological qualities, 12 papers were selected for this study, while 531 articles were searched. The overall diagnostic sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and area under the receiver operating characteristic curve (AUC-ROC) were used to evaluate the diagnostic value of HE4 for ovarian cancer using the Meta-DiSc statistical software. RESULTS: There were 2607 subjects included in this meta-analysis. The sensitivity, specificity, LR+ and LR- (95% confidence interval) of HE4 was 0.800 (0.770-0.827), 0.916 (0.902-0.929), 10.271 (6.982-15.109) and 0.228 (0.181-0.287), respectively. The area under the summary receiver operating characteristic (sROC) curve of HE4 was 0.946. The index of Q* was 0.885. CONCLUSIONS: HE4 was found to be better than CA125 as an auxiliary indicator for the diagnosis of ovarian cancer in terms of better sensitivity, specificity, LR+ and LR-.

Diagnostic value of pro-gastrin-releasing peptide for small cell lung cancer: a meta-analysis.

BACKGROUND: Lung cancer, of which 15%-20% is small cell lung cancer, is the leading cause of cancer mortality and shows a high incidence worldwide. While pro-gastrin-releasing peptide (ProGRP) has been reported as a predictive diagnostic factor, it has not been widely accepted because of inconsistent conclusions. The aim of this study was to systematically evaluate ProGRP as the diagnostic standard for small cell lung cancer. METHODS: All published studies on ProGRP in the diagnosis of small cell lung cancer from January 1994 to April of 2010 were retrieved. By measuring methodological qualities, 11 papers were selected for this study. The overall diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate ProGRP as the diagnostic standard for small cell lung cancer using Meta DiSc statistical software. RESULTS: There were 5146 subjects included in this meta-analysis. The sensitivity and specificity (95% confidence interval) of ProGRP was 0.716 (0.688-0.743) and 0.921 (0.909-0.932), respectively. The area under the summary receiver operating characteristic curve of ProGRP was 0.9236. The index of Q* was 0.8575. CONCLUSIONS: ProGRP has better sensitivity and high specificity as an auxiliary indicator for the diagnosis of small cell lung cancer.

Scale invariance of human electroencephalogram signals in sleep.

In this paper, we investigate the dynamical properties of electroencephalogram (EEG) signals of humans in sleep. By using a modified random walk method, we demonstrate that scale-invariance is embedded in EEG signals after a detrending procedure is applied. Furthermore, we study the dynamical evolution of the probability density function (PDF) of the detrended EEG signals by nonextensive statistical modeling. It displays a scale-independent property, which is markedly different from the usual scale-dependent PDF evolution and cannot be described by the Fokker-Planck equation.

[Hearing impairment in senile dementia of Alzheimer's type].

OBJECTIVE: To evaluate the pure tone hearing threshold and word recognition score of senile dementia of the Alzheimer's disease (AD) patients, and to analyze the relationship between hearing loss and the cognition impairment. METHODS: Pure tone audiometry, word recognition score (WRS), acoustic immittance and auditory brainstem response (ABR) are used to evaluate the auditory function of 43 patients with AD and 50 subjects of the control group. The confounding factors are controlled. RESULTS: The average age of 43 dementia patients was 72.7 +/- 6.4, and 69.7% was female. Bilateral hearing thresholds are similar in all subjects. All indices but Mini-mental scale of equastionnaire (MMSE) of patients and control group were not statistically different. There was no significant difference in pure tone audiometry (PTA), PTA2 (dB HL, mean +/- s) and WRS (%, mean +/- s) between the two groups (P > 0.05), therefore the hearing threshold of AD group (PTA = 26.3 +/- 8.5, PTA2 = 29.1 +/- 8.7, WRS = 85.5 +/- 15.5) is lower than that of control group (PTA = 23.2 +/- 10.6, PTA2 = 26.2 +/- 11.8, WRS = 87.6 +/- 16.8). No significant difference was found between the two groups in audiometry reliability, acoustic immittance and ABR (P < 0.05). CONCLUSION: No significant difference was found between the peripheral hearing dysfunction of AD patients and that normal elderly people, i.e., PTA, PTA2 and WRS were not related to MMSE.