Synthesis of Chiral Endocyclic Allenes and Alkynes via Pd-Catalyzed Asymmetric Higher-Order Dipolar Cycloaddition.

A Pd-catalyzed asymmetric higher-order dipolar cycloaddition between allenyl carbonates and azadienes is achieved by exploiting novel alkylidene-π-allyl-Pd dipoles. This research provides a modular platform for the synthesis of challenging chiral endocyclic allenes bearing a medium-sized heterocyclic motif and a centrally chiral stereocenter in good yields with high enantio- and diastereoselectivities (29 examples, up to 97% yield, 97:3 er and >19:1 dr). Experimental and computational studies elucidate the possible reaction mechanism and the observed stereochemical results. Based on the mechanistic understanding, a new π-propargyl-Pd dipole was designed to further extend the success of the higher order dipolar cycloaddition strategy to the synthesis of 10-membered endocyclic alkynes from propargyl carbonates and azadienes (13 examples, up to 98% yield and 94.5:5.5 er).

Rational design of anthocyanidins-directed near-infrared two-photon fluorescent probes.

Recently, two-photon fluorescent probes based on anthocyanidin molecules have attracted extensive attention due to their outstanding photophysical properties. However, there are only a few two-photon excited fluorescent probes that really meet the requirements of relatively long emission wavelengths (>600 nm), large two-photon absorption (TPA) cross-sections (300 GM), significant Stokes shift (>80 nm), and high fluorescence intensity. Herein, the photophysical properties of a series of anthocyanidins with the same substituents but different fluorophore skeletons are investigated in detail. Compared with b-series molecules, a-series molecules with a six-membered ring in the backbone have a slightly higher reorganization energy. This results in more energy loss upon light excitation, enabling the reaction products to detect NTR through a larger Stokes shift. More importantly, there is very little decrease in fluorescence intensity as the Stokes shift increases. These features are extremely valuable for high-resolution NTR detection. In light of this, novel 2a-n (n = 1-5) compounds are designed, which are accomplished by inhibiting the twisted intramolecular charge transfer (TICT) effect through alkyl cyclization, azetidine ring and extending π conjugation. Among them, 2a-3 gains a long emission spectrum (λem = 691.4 nm), noticeable TPA cross-section (957 GM), and large Stokes shift (110 nm), indicating that it serves as a promising candidate for two-photon fluorescent dyes. It is hoped that this work will offer some insightful theoretical direction for the development of novel high performance anthocyanin fluorescent materials.

Bioelectricity generation from the decolorization of reactive blue 19 by using microbial fuel cell.

Microbial fuel cell (MFC) was compared to conventional biological techniques for decolorization of anthraquinone dye, reactive blue 19 (RB19) with simultaneous electricity generation. With 50 mg/L of RB19 in the anode chamber as a fuel, the MFC achieved 89% decolorization efficiency of RB19 within 48 h, compared with 51 and 55% decolorization efficiency achieved by aerobic and anaerobic techniques, respectively. The cyclic voltammetry results showed that RB19 could promote the electron transfer and redox reaction on the surface of anode. The RB19 decolorization process can be described by first-order kinetics, and the decolorization rate decreased with the increase of RB19 concentration. The high-throughput 16S rRNA sequencing analysis indicated significant microbial community shift in the MFC. At phylum level, the majority of sequences belong to Proteobacteria, accounting from 23 to 84% of the total reads in each bacterium community. At genus level, the MFC contained two types of microorganisms in general such as electrochemically active and decolorization bacteria. Overall, MFC is an effective method for anthraquinone dye treatment with simultaneous energy recovery. The 16S rRNA revealed that there were two major functioning microbial communities in the MFC such as electricity-producing and RB19-degrading bacteria which synergistically worked on RB19 degradation.

[The China National GeneBank─owned by all, completed by all and shared by all].

Genetic resources are important national strategic resources. Their preservation, protection and rational utilization form a solid foundation to guarantee national security and to build national competitiveness for the future. Due to a relatively late starting point, China is actively catching up with global peers in storing genetic samples and data. In view of this, in 2011 China approved a plan to build its first nation-level comprehensive gene bank, the China National GeneBank (CNGB), and entrusted BGI-Research to implement its construction and operation. It is China's first gene bank for "reading, writing and storing" bioresources. In this paper, we summarize the development of influential platforms at home and abroad, and focus on CNGB's position, mission, and its structure of "Three Banks and Two Platforms". CNGB launched its official operation in September 2016 and aims to develop a world-class, non-profit and strategic platform that supports science and technology development. It has built capacities to store tens of millions of traceable samples and to analyze handreds of thousanda of WGS each year. It has also set up China's first Pb-level digitalization platform and a high-efficient synthesis platform with a production rate of ten million bases per year. Based on such capacities, CNGB has established its open sharing mechanism for biological samples and data, provided public platform services for life science research, and achieved initial results in supporting innovation and development of the bio-industry.

IL1R1 and IL1R2 polymorphisms were associated with tuberculosis risk: A pilot study.

BACKGROUND: Interleukin (IL)-1 has been reported to be involved in the development of tuberculosis (TB). IL1R1 and IL1R2 encode a cytokine receptor that belongs to the IL-1 receptor family. However, few studies have reported on the polymorphisms of IL1R1 and IL1R2 in TB patients. METHODS: We investigated nine single-nucleotide polymorphisms (SNPs) in IL1R1 and IL1R2 in 300 TB patients and 300 controls, aiming to evaluate their association with TB risk. Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for age and gender. RESULTS: On comparing the allele frequencies of candidate SNPs, we found that the minor allele 'A' of rs4851527 in IL1R2 was associated with a decreased risk of TB, whereas the minor alleles of rs10490571, rs956730 and rs3917225 in IL1R1 were associated with an increased risk of TB (p < 0.05). In the genetic model analysis, we found that the allele 'A' of rs4851527 was correlated with a decreased risk of TB in a log-additive model, whereas the minor alleles of rs719250, rs3218977, rs10490571, rs956730 and rs3917225 were correlated with an increased risk of TB in dominant and log-additive models (p < 0.05). Additionally, we found three haplotypes that were associated with an increased risk of TB: TGCT and TGTT haplotypes constructed by rs11674595, rs4851527, rs719250 and rs3218896, as well as GA haplotype constructed by rs3218977 and rs2072472 (p < 0.05). CONCLUSIONS: Our data shed new light on the association between genetic polymorphisms of IL1R1 and IL1R2 and TB susceptibility in the Chinese Han population.

Selective Etching Induced Synthesis of Hollow Rh Nanospheres Electrocatalyst for Alcohol Oxidation Reactions.

The hollow noble metal nanostructures have attracted wide attention in catalysis/electrocatalysis. Here a two-step procedure for constructing hollow Rh nanospheres (Rh H-NSs) with clean surface is described. By selectively removing the surfactant and Au core of Au-core@Rh-shell nanostructures (Au@Rh NSs), the surface-cleaned Rh H-NSs are obtained, which contain abundant porous channels and large specific surface area. The as-prepared Rh H-NSs exhibit enhanced inherent activity for the methanol oxidation reaction (MOR) compared to state-of-the-art Pt nanoparticles in alkaline media. Further electrochemical experiments show that Rh H-NSs also have high activity for the electrooxidation of formaldehyde and formate (intermediate species in the course of the MOR) in alkaline media. Unfortunately, Rh H-NSs have low electrocatalytic activity for the ethanol and 1-propanol oxidation reactions in alkaline media. All electrochemical results indicate that the order of electrocatalytic activity of Rh H-NSs for alcohol oxidation reaction is methanol (C1 ) > ethanol (C2 ) > 1-propanol (C3 ). This work highlights the synthesis route of Rh hollow nanostructures, and indicates the promising application of Rh nanostructures in alkaline direct methanol fuel cells.

Galla chinensis Compounds Remineralize Enamel Caries Lesions in a Rat Model.

OBJECTIVES: To investigate the effect of Galla chinensis chemical compounds on enamel caries remineralization in rats. METHODS: A total of 40 rats were inoculated with Streptococcus sobrinus 6715 and fed a cariogenic diet (Keyes 2000). The rats were randomly divided into 4 groups and treated topically twice a day with each of the following extracts (or control) for 5 weeks: distilled and deionized water (DDW, negative control); 1,000 ppm NaF (positive control); 4,000 ppm G. chinensis crude aqueous extract (GCE), or 4,000 ppm gallic acid (GA). After the experimental period, Keyes' caries diagnosis and scoring technique was applied as a preliminary evaluation on the molar teeth. For more accurate remineralization data, the residual enamel volume of the first molar and the mineral density (MD) of the enamel were further analyzed by micro-CT. RESULTS: The severity of molar enamel caries decreased in the following order of treatment groups: DDW > GA > GCE > NaF (p < 0.05). In addition, the residual first molar enamel volume and MD values increased in the order of DDW, GA, GCE and NaF treatment groups (p < 0.05). In most molars, remineralization layers were observed on the surface of lesions. CONCLUSION: G. chinensis compounds remineralize enamel caries lesions in a rat model.

[Long-term exposure to PM2.5 from automobile exhaust results in reproductive dysfunction in male rats].

OBJECTIVE: To explore the effects of long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust on the reproductive function of Sprague Dawley (SD) rats. METHODS: Forty-five male SD rats, weighing 80 - 94 g and aged 28 days, were randomly assigned to receive intra-tracheal administration of 0.9% normal saline (control group, n = 15), PM2. 5 at 2 µg per 100 g body weight per day (low-dose PM2.5 group, n = 15), and PM2.5 at 16 µg per 100 g body weight per day (high-dose PM2.5 group, n = 15), qd, for 60 successive days. After the last 24-hour exposure, 10 rats were taken from each group for copulation with normal female ones, while the others were sacrificed, their testes removed for sperm count and deformity, pathological examination, and determination of the Connexin43 expression. RESULTS: The conception rate was significantly decreased in the low- and high-dose PM2.5 groups as compared with that of the control (70% and 50% vs 100%), and so were the sperm count and quality. The rats in the PM2.5-exposed groups showed significantly disordered histological structure of the seminiferous tubules, reduced sperm count in the testicular lumen, some exfoliated secondary spermatocytes, downregulated Connexin43 expression in the testis, and damaged blood-testis barrier. CONCLUSION: Long-term exposure to PM2.5 from automobile exhaust damages the reproductive function of male SD rats.

[Using Raman spectrum analysis to research corrosive productions occurring in alloy of ancient bronze wares].

The present paper analyzes the interior rust that occurred in bronze alloy sample from 24 pieces of Early Qin bronze wares. Firstly, samples were processed by grinding, polishing and ultrasonic cleaning-to make a mirror surface. Then, a confocal micro-Raman spectrometer was employed to carry out spectroscopic study on the inclusions in samples. The conclusion indicated that corrosive phases are PbCO3 , PbO and Cu2O, which are common rusting production on bronze alloy. The light-colored circular or massive irregular areas in metallographic structure of samples are proved as Cu2O, showing that bronze wares are not only easy to be covered with red Cu2O rusting layer, but also their alloy is easy to be eroded by atomic oxygen. In other words, the rust Cu2O takes place in both the interior and exterior parts of the bronze alloy. In addition, Raman spectrum analysis shows that the dark grey materials are lead corrosive products--PbCO3 and PbO, showing the corroding process of lead element as Pb -->PbO-->PbCO3. In the texture of cast state of bronze alloy, lead is usually distributed as independent particles between the different alloy phases. The lead particles in bronze alloy would have oxidation reaction and generate PbO when buried in the soil, and then have chemical reaction with CO3(2-) dissolved in the underground water to generate PbCO3, which is a rather stable lead corrosive production. A conclusion can be drawn that the external corrosive factors (water, dissolved oxygen and carbonate, etc) can enter the bronze ware interior through the passageway between different phases and make the alloy to corrode gradually.

Identification of a new species of Gyrodactylus von Nordmann, 1832 (Monogenoidea Gyrodactylidae) isolated from Diptychus maculatus in Yarkand River, Xinjiang, China.

To investigate Gyrodactylus infection of fish in the river system of Xinjiang (China), Gyrodactylus individuals were isolated from specimens of Diptychus maculatus. Morphological characterization and phylogenetic analysis based on ITS1-5.8S-ITS2 rDNA locus revealed that the gyrodactylids belong to new species. Gyrodactylus diptychi n. sp. differs significantly in the morphology of the haptoral structures from 12 known species of Gyrodactylus found in fishes of the subfamily Schizothoracinae. In particular, G. diptychi n. sp. has a relatively short dorsal bar with thick and large ends, flat and straight hamuli roots, and small ventral bar processes. Furthermore, G. diptychi n. sp. is the only representative of Gyrodactylus found on D. maculatus. Using the BLASTn search of ITS1-5.8S-ITS2 rDNA sequences in GenBank and the Bayesian Information and Maximum Likelihood methods, we constructed phylogenetic trees for G. diptychi n. sp. As a result, our studies clearly identified that G. diptychi n. sp. was the first Gyrodactylus monogenean isolated from D. maculatus and a new species belonged to the subgenus Limnonephrotus.

Complete mitochondrial genomes of Dactylogyrus crucifer and Dactylogyrus zandti reveal distinct patterns of codon usage within Dactylogyrus.

Monogeneans of the genus Dactylogyrus Diesing, 1850, the largest genus in the family Dactylogyridae, mostly parasitize the gills of cyprinoid hosts; however, only 3 Dactylogyrus' mitochondrial genomes (mitogenomes) are studied so far. The aim of this research is to extend our understanding of the mitogenomes of Dactylogyrus. We sequenced the mitogenomes of D. crucifer and D. zandti isolated from Rutilus rutilus and Abramis brama orientalis in northwest China, and then we compared these mitogenomes with other monogeneans. We used Illumina NovaSeq to sequence the entire mitochondrial genomes of D. crucifer and D. zandti and characterized the mitogenomes to understand the gene structure, gene identity, the secondary structures of the 22 tRNA genes, and relative synonymous codon usage. We used the analytic Bayesian Information and Maximum Likelihood methods to determine their associated phylogenetic trees. The mitogenomes of D. crucifer and D. zandti were 14,403 and 18,584 bp, respectively. Organization and positioning of these genes were in accordance with Dactylogyrus lamellatus and Dactylogyrus tuba. The nucleotide composition of Dactylogyridae was different from other families of Monogenea, and the A+T count of genus Dactylogyrus (54 - 58.4 %) was lower than other genus species of the family Dactylogyridea (63.9 - 78.4 %) in protein-coding genes. Dactylogyrus members displayed a codon usage bias. The relative synonymous codon used by Dactylogyrus was not conserved and was lower than other monogeneans. The codon use patterns of closely-related species isolated from closely-related hosts were identical. Phylogenetic analyses using mitogenomic dataset produced Dactylogyrus isolated from host subfamily Leuciscinae formed a sister-group. Our results contributed significantly to an increased database of mitogenomes, more than 50 %, for Dactylogyrus that may help future studies of mitochondrial genes and codon uses for the analysis of monogenean phylogenetics.

Rhodium metallene-supported platinum nanocrystals for ethylene glycol oxidation reaction.

Low-temperature fuel cells have great application potential in electric vehicles and portable electronic devices, which need advanced electrocatalysts. Controlling the composition and morphology of electrocatalysts can effectively improve their catalytic performance. In this work, a Rh metallene (Rhlene)-supported Pt nanoparticle (Pt/Rhlene) electrocatalyst is successfully synthesized by a simple chemical reduction method, in which ultra-small Pt nanoparticles are uniformly attached to the Rhlene surface due to the high surface area of Rhlene. Pt/Rhlene reveals a 3.60-fold Pt-mass activity enhancement for the ethylene glycol oxidation reaction in alkaline solution compared with commercial Pt black, and maintains high stability and excellent poisoning-tolerance during electrocatalysis, owing to the specific physical/chemical properties of Rhlene. The superior electrocatalytic performance of Pt/Rhlene may open an avenue to synthesize other metallene-supported noble metal nanoparticle hybrids for various electrocatalytic applications.

IgA nephropathy to proliferative glomerulonephritis with monoclonal IgAκ deposits: a pattern switch.

We report the case of a 31-year-old male who presented with repeated episodes of nephritic-nephrotic syndrome in concomitance with infection. IgA was diagnosed and was initially responsive to treatment with immunosuppressors but further disease flare did not respond to treatment. Based on three consecutive renal biopsies over 8 years, a pattern switch from endocapillary proliferative IgA nephropathy to membranous proliferative glomerulonephritis with monoclonal IgAκ deposits was observed. Bortezomib-dexamethasone combination therapy finally led to a favorable renal response. This case provides new insights into the pathophysiological mechanisms of proliferative glomerulonephritis with monoclonal immunoglobin deposits (PGNMID), highlighting the importance of repeat renal biopsies and routine evaluation of monoclonal immunoglobin deposits in proliferative glomerulonephritis with refractory nephrotic syndrome.

Role of SOCS1 in tumor progression and therapeutic application.

SOCS1, a prototype molecule of the SOCS family, was initially defined as a suppressor of cytokine signaling. The molecular mechanisms of SOCS1-mediated functions have been subsequently identified by studies using gene knockout mice and gene silencing technology. As part of a negative feedback regulation, SOCS1 downregulates cytokine signaling through direct inhibition of the JAK tyrosine kinase and the signaling cascade of activated cytokine receptors, thereby attenuating cytokine-initiated signal transduction. Moreover, other studies have demonstrated that SOCS1 also downregulates TLR signaling through direct and indirect mechanisms. Both cytokine receptor and TLR signaling pathways mediate important functions in survival, maturation and differentiation of various types of cells and in the regulation of immune function. Abnormal expression of SOCS1 in tumor cells has been detected in various human cancers, where it is associated with dysregulation of cytokine receptor and TLR signaling to promote cell transformation. Recent studies on the function of SOCS1 in tumor cells have revealed its novel role in carcinogenesis. In this review, we will focus on the mechanism of action of SOCS1 in both tumor cells and antigen-presenting cells in the tumor microenvironment. The potential of using SOCS1 as a diagnostic marker and therapeutic target in tumor diagnosis, prognosis and treatment is discussed.

How do tumor stem cells actively escape from host immunosurveillance?

Tumor stem cells (TSCs) are considered as the "seeds" in tumor development, metastasis and recurrence. Despite the various immunosurveillance mechanisms in the host, TSCs may possess the phenotypic and functional properties to evade host immunosurveillance and immune-mediated rejection in immunologically intact individuals. The mechanisms of TSC recognition and their consequent destruction are actively disturbed by various processes, including altered immunogenicity of TSCs, production of TSC-derived regulatory molecules, and interaction of TSCs with tumor-infiltrating immune cells. In addition to these TSC-mediated mechanisms, the diverse mesenchymal cells and cytokines in the tumor microenvironment are contribute to TSC immune escape. Recent mechanistic studies provide a more comprehensive understanding of TSCs in the biology, prevention, and therapy of solid tumors. This review will focus on the latest findings for mechanisms underlying TSCs' escape from the attack of immune system.

MiR-371a-5p Positively Associates with Hepatocellular Carcinoma Malignancy but Sensitizes Cancer Cells to Oxaliplatin by Suppressing BECN1-Dependent Autophagy.

Oxaliplatin (OXA)-based chemotherapy demonstrates active efficacy in advanced hepatocellular carcinoma (HCC), while resistance development limits its clinical efficacy. Thus, identifying resistance-related molecules and underlying mechanisms contributes to improving the therapeutic efficacy of HCC patients. MicroRNA-371a-5p (MiR-371a-5p) fulfills an important function in tumor progression. However, little is known about the effect of miR-371a-5p on chemotherapy response. In this study, quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were used to determine the expression levels of miR-371a-5p, BECN1 and autophagy-related proteins in HCC cells, tissues and serum. The luciferase reporter assay was used to assess the directly suppressive effect of miR-371a-5p on BECN1 mRNA translation. Moreover, gain- and loss-of-function assays and rescue assays were used to evaluate the mediated effect of BECN1-dependent autophagy on the role of miR-371a-5p in the response of HCC cells to OXA. We found that miR-371a-5p was significantly up-regulated in HCC tissues and serum from patients, whereas BECN1 protein was down-regulated in HCC tissues compared to the corresponding controls. We also found that there was a negative correlation between the two molecules in HCC tissues. In addition, we found that miR-371a-5p expression was positively associated with malignant characteristics of HCC and BECN1 protein expression is negatively associated. Contrary to this, we found that miR-371a-5p enhances and BECN1 attenuates the response of HCC cells to OXA. Importantly, the enhanced effect of miR-371a-5p on the response of HCC cells to OXA could be reduced by re-expression of non-targetable BECN1, and then the reduced effect was restored following bafilomycin A treatment. Taken together, we identified a dual role of miR-371a-5p in HCC malignant characteristics and the response of HCC cells to oxaliplatin. Importantly, we reveal that miR-371a-5p enhances oxaliplatin response by target suppression of BECN1-dependent autophagy.

[Expression of indoleamine 2, 3-dioxygenase and its correlation with prognosis in breast cancer patients].

OBJECTIVE: To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis. METHODS: The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry. RESULTS: The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO (P > 0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r = 0.659, P < 0.05). CONCLUSIONS: Expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression.

[Distribution and evolution of simple repeats in the mtDNA D-loop in mammalian].

Simple sequence repeats (SSR) distribute extensively in genomes of all organisms, but the molecular mechanism underlined is poorly understood. In this study, we characterized distribution and biological significance of the simple repetitive DNA sequences in the D-loop region in mitochondria DNA of 256 mammal species, and classified the mammal carriers into three groups including 53 species with hexanucleotide repeats, 104 species with other types of simple repeats (>6 bp) and 99 species without any repeat sequences, respectively. Furthermore, we found that the hexanucleotide repeats dispersed significantly in the interval space between CSB1 and CSB2, while other repeats dispersed mainly in the termination region, central conserved region and the conserve sequence block (CSB) regions. In addition, comparison on the base composition and the DNA contexts of the central conserved region, CSB1, CSB2, and CSB3 revealed a lack of significant differences in similarity among different species with or without repeat sequences. Moreover, a phylogenetic analysis with 256 mammal species using N-J method suggested loss of the repeat sequences in mammals in evolution.

[Localization of the bronchial air leakage in pneumothorax by injection of human albumin foam].

OBJECTIVE: To evaluate the efficacy and safety of a new method to determine the bronchus for air leakage in pneumothorax by injection of human albumin foam. METHODS: In 29 cases with pneumothorax, the bronchus responsible for air leakage was localized by injecting foam of human albumin into target bronchus under direct view of bronchoscopy. RESULTS: The bronchus for air leakage was successfully localized in all the 29 cases of pneumothorax. The average time for locating (from injection of the foam to the localization of the bronchus) was (4.0 ± 1.2) min, and the average amount of 20% human albumin used was (8.0 ± 2.6) ml for each patient. The air leakage was treated accordingly, and occlusion by fibrin glue was successfully carried out in 21 cases and by OB glue in 8 cases. Severe cough was noted in 6, fever in 4, thoracic bleeding in 4 cases, and chest pain in 1 case. CONCLUSION: Injection of human albumin foam into target bronchus under bronchoscopy was a simple, safe and effective method for the localization of the bronchus for air leakage in pneumothorax.