Na2S-Mediated One-Pot Selective Deoxygenation of α-Hydroxyl Carbonyl Compounds including Natural Products.

A practical method for the deoxygenation of α-hydroxyl carbonyl compounds under mild reaction conditions is reported here. The use of cheap and easy-to-handle Na2S·9H2O as the reductant in the presence of PPh3 and N-chlorosuccinimide (NCS) enables the selective dehydroxylation of α-hydroxyl carbonyl compounds, including ketones, esters, amides, imides and nitrile groups. The synthetic utility is demonstrated by the late-stage deoxygenation of bioactive molecule and complex natural products.

Release of Leu-Pro-Pro from corn gluten meal by fermentation with a Lactobacillus helveticus strain.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitory peptides are potential alternatives to the synthetic ACE inhibitory drugs, but the in vivo antihypertensive effects of most of them have not been confirmed. The tripeptide Leu-Pro-Pro (LPP) is one of the few peptides that have been proved clinically effective in reducing the blood pressure of hypertensive patients and casein is currently its major source. LPP is contained in multiple fractions of zein, and corn gluten meal (CGM) is hence a potential new source of LPP. For this purpose, CGM was fermented with a Lactobacillus helveticus strain and the medium composition was optimized; the decoloration of the resultant hydrolysate was investigated as well. RESULTS: LPP could be successfully released from CGM by fermentation with the strain Lactobacillus helveticus CICC 22536. The highest LPP content and protein recovery of 561 mg kg-1 and 14.92% occurred in the medium containing 20 g L-1 glucose, 15 g L-1 beef extract, 60 g L-1 CGM, 10 g L-1 CaCO3 , 0.5 g L-1 NaCl, and inoculation amount 6%. The supplementation of Flavourzyme® further improved the two parameters to 662 mg kg-1 and 36.94%, respectively. The permeate of the hydrolysate after ultrafiltration through a 5 kDa membrane could be effectively decolored by the macroporous resin XAD-16 without notable protein loss, and its LPP content was further boosted to 743 mg kg-1 . CONCLUSION: CGM is a potential new source of LPP and its ultrafiltered and decolored hydrolysate could be used to develop new antihypertensive functional foods. © 2021 Society of Chemical Industry.

Collaborative governance effects of carbon market on GHG and air pollutants emission reduction in 3E model -- analysis based on System Dynamics.

The carbon market is regarded as one of the important means to achieve China's dual carbon target. It has ancillary effect for reducing air pollution while regulating carbon emissions since climate change and air pollution share the same origin and homology. Research on how to design the carbon market mechanism in order to maximize the synergistic effect of reducing greenhouse gas and air pollution will have a very important practical impact for China. This study conducts a theoretical analysis of the collaborative emission reduction path of China's carbon market, and constructs an Energy-Economy-Environment (3E) model of the collaborative emission reduction effect of carbon trading system based on System Dynamics. After analyzing the feedback path of the core cycle of the model and verifying its performance, three main policy factors in the carbon market are explored, and their effects under the dual objectives of emission control and economic development are comprehensively evaluated. This study suggests that the exploration of the potential of carbon market for collaborative governance should be accelerated, and ensure the orderly expansion of coverage and precise setting of limits, so as to ensure the smooth achievement of carbon reduction targets while guaranteeing the social and economic development.

Nickel(II)-catalyzed highly selective 1,2-diborylation of non-activated monosubstituted alkenes.

A practical method for 1,2-diborylation of non-activated monosubstituted alkenes via nickel catalysis has been developed. The protocol features high functional group tolerance and can be applied for the formal synthesis of drugs and modification of natural product derivatives. Preliminary mechanistic studies imply the involvement of a Ni(II) catalytic cycle.

Role of transcribed ultraconserved regions in gastric cancer and therapeutic perspectives.

Gastric cancer (GC) is the fourth leading cause of cancer-related death. The occurrence and development of GC is a complex process involving multiple biological mechanisms. Although traditional regulation modulates molecular functions related to the occurrence and development of GC, the comprehensive mechanisms remain unclear. Ultraconserved region (UCR) refers to a genome sequence that is completely conserved in the homologous regions of the human, rat and mouse genomes, with 100% identity, without any insertions or deletions, and often located in fragile sites and tumour-related genes. The transcribed UCR (T-UCR) is transcribed from the UCR and is a new type of long noncoding RNA. Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC, revealing a new mechanism underlying GC. Therefore, this article aims to review the relevant research on T-UCRs in GC, as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC, to provide new strategies for GC diagnosis and treatment.

Intestine-targeted delivery potency of O-carboxymethyl chitosan-coated layer-by-layer microcapsules: An in vitro and in vivo evaluation.

The intestine-targeted delivery performance of the gum Arabic (GA) - O-carboxymethyl chitosan (OCMC) microcapsules prepared by layer-by-layer (LbL) assembly and genipin crosslinking was evaluated by using an acid-susceptible compound omeprazole as the model. Confocal laser scanning microscope observation revealed that spherical microcapsules with the core-shell structure were successful fabricated. Genipin crosslinking did not affect the microencapsulation yield or drug load, but significantly decreased the particle size and positive charge of the microcapsules, and increased their stability against disintegration in the simulated gastric fluid. Pharmacokinetic analysis indicated that entrapment by GA - OCMC LbL assembly greatly improved the bioavailability of omeprazole and crosslinking by 0.1 mg/mL genipin led to the highest value of 8.76 relative to the control formulation. It was concluded that the GA - OCMC LbL microcapsules could be used for the oral delivery of nutraceuticals and its delivery performance could be tailored by varying the genipin crosslinking degree.

FRS: A simple knowledge graph embedding model for entity prediction.

Entity prediction is the task of predicting a missing entity that has a specific relation-ship with another given entity. Researchers usually use knowledge graphs embedding(KGE) methods to embed triples into continuous vectors for computation and perform the tasks of entity prediction. However, KGE models tend to use simple operations to refactor entities and relationships, resulting in insufficient interaction of components of knowledge graphs (KGs), thus limiting the performance of the entity prediction model. In this paper, we propose a new entity prediction model called FRS(Feature Refactoring Scoring) to alleviate the problem of insufficient interaction and solve information incom-pleteness problems in the KGs. Different from the traditional KGE methods of directly using simple operations, the FRS model innovatively provides the procedure of feature processing in the entity prediction tasks, realizing the alignment of entities and relationships in the same feature space and improving the performance of entity prediction model. Although FRS is a simple three-layer network, we find that our own model outperforms state-of-the-art KGC methods in FB15K and WN18. Through extensive experiments on FRS, we discover several insights. For example, the effect of embedding size and negative candidate sampling probability on experimental results is in reverse.

INI1 induces interferon signaling and spindle checkpoint in rhabdoid tumors.

PURPOSE: Rhabdoid tumors are rare but aggressive pediatric malignancies characterized by biallelic loss of INI1/hSNF5. Reintroduction of INI1 causes cell arrest and senescence in rhabdoid cells. Our purpose was to identify INI1-downstream genes and to determine their functional and therapeutic significance for rhabdoid tumors. EXPERIMENTAL DESIGN: INI1 downstream targets in rhabdoid cells were identified using a cDNA microarray analysis and the expression of selected INI1 targets was confirmed by quantitative reverse transcription-PCR, Western analysis, and/or immunohistochemical analysis of rhabdoid cells and primary rhabdoid tumors. To determine the functional significance of downstream targets, activated targets of INI1 were induced and repressed targets of INI1 were knocked down (by using RNA interference) in rhabdoid cells, in the absence of INI1. Consequence of altered expression of INI1 downstream targets for rhabdoid cell survival, cell cycle, and apoptosis was assessed. RESULTS: Microarray studies indicated that INI1 activated IFN-stimulated genes at early time points and senescence markers at late time points and repressed mitotic genes such as Polo like kinase 1 (PLK1), selectively in rhabdoid cells. Treatment of rhabdoid cells with recombinant IFNs resulted in induction of IFN-stimulated genes, G1 arrest, and flat cell formation. PLK1 was overexpressed in primary human and mouse rhabdoid tumors. RNA interference-mediated knock down of PLK1 in rhabdoid cells resulted in mitotic arrest, aberrant nuclear division, decreased survival, and induction of apoptosis. CONCLUSIONS: Targeting downstream effectors of INI1 such as IFN pathway and mitotic genes leads to antiproliferative effects in rhabdoid cells. IFN treatment and down-modulation of PLK1 constitute potential novel therapeutic strategies for rhabdoid tumors.

Cell cycle arrest and repression of cyclin D1 transcription by INI1/hSNF5.

INI1/hSNF5 is a component of the ATP-dependent chromatin remodeling hSWI/SNF complex and a tumor suppressor gene of aggressive pediatric atypical teratoid and malignant rhabdoid tumors (AT/RT). To understand the molecular mechanisms underlying its tumor suppressor function, we studied the effect of reintroduction of INI1/hSNF5 into AT/RT-derived cell lines such as MON that carry biallelic deletions of the INI1/hSNF5 locus. We demonstrate that expression of INI1/hSNF5 causes G(0)-G(1) arrest and flat cell formation in these cells. In addition, INI1/hSNF5 repressed transcription of cyclin D1 gene in MON, in a histone deacetylase (HDAC)-dependent manner. Chromatin immunoprecipitation studies revealed that INI1/hSNF5 was directly recruited to the cyclin D1 promoter and that its binding correlated with recruitment of HDAC1 and deacetylation of histones at the promoter. Analysis of INI1/hSNF5 truncations indicated that cyclin D1 repression and flat cell formation are tightly correlated. Coexpression of cyclin D1 from a heterologous promoter in MON was sufficient to eliminate the INI1-mediated flat cell formation and cell cycle arrest. Furthermore, cyclin D1 was overexpressed in AT/RT tumors. Our data suggest that one of the mechanisms by which INI1/hSNF5 exerts its tumor suppressor function is by mediating the cell cycle arrest due to the direct recruitment of HDAC activity to the cyclin D1 promoter thereby causing its repression and G(0)-G(1) arrest. Repression of cyclin D1 gene expression may serve as a useful strategy to treat AT/RT.

Genetic source tracking of an anthrax outbreak in Shaanxi province, China.

BACKGROUND: Anthrax is an acute zoonotic infectious disease caused by the bacterium known as Bacillus anthracis. From 26 July to 8 August 2015, an outbreak with 20 suspected cutaneous anthrax cases was reported in Ganquan County, Shaanxi province in China. The genetic source tracking analysis of the anthrax outbreak was performed by molecular epidemiological methods in this study. METHODS: Three molecular typing methods, namely canonical single nucleotide polymorphisms (canSNP), multiple-locus variable-number tandem repeat analysis (MLVA), and single nucleotide repeat (SNR) analysis, were used to investigate the possible source of transmission and identify the genetic relationship among the strains isolated from human cases and diseased animals during the outbreak. RESULTS: Five strains isolated from diseased mules were clustered together with patients' isolates using canSNP typing and MLVA. The causative B. anthracis lineages in this outbreak belonged to the A.Br.001/002 canSNP subgroup and the MLVA15-31 genotype (the 31 genotype in MLVA15 scheme). Because nine isolates from another four provinces in China were clustered together with outbreak-related strains by the canSNP (A.Br.001/002 subgroup) and MLVA15 method (MLVA15-31 genotype), still another SNR analysis (CL10, CL12, CL33, and CL35) was used to source track the outbreak, and the results suggesting that these patients in the anthrax outbreak were probably infected by the same pathogen clone. CONCLUSIONS: It was deduced that the anthrax outbreak occurred in Shaanxi province, China in 2015 was a local occurrence.

Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens.

Androgens via the androgen receptor (AR) play crucial roles in prostate physiology and pathophysiology. These androgen actions can be either inhibited or potentiated by estrogens. The mechanisms of these seemingly opposing estrogen effects are unclear. We studied the effects of estrogens on the modulation of androgen induction of prostate specific antigen (PSA) gene expression and prostate tumor cell growth. Cotransfection analyses in CV-1, DU-145, and PC-3 cells showed that dihydrotestosterone (DHT)-induced PSA transcription activity was inhibited by 17beta-estradiol, diethylstilbestrol, ICI182780, and 17alpha-estradiol, but not by tamoxifen via estrogen receptor alpha (ERalpha). In the presence of ERbeta, 17beta-estradiol and diethylstilbestrol had no significant effect, while 17alpha-estradiol inhibited and ICI182780 and tamoxifen potentiated DHT action. When both ERalpha and ERbeta were present, all ER-ligands except tamoxifen inhibited DHT action. The inhibition of DHT action by 17beta-estradiol via ERalpha was mainly dependent on the DNA binding domain, while the 17alpha-estradiol effect was mainly dependent on the ERalpha carboxyl terminus. Treatment with DHT in LAPC-4 prostate tumor cells that express a wild-type AR and both ERbeta and ERalpha greatly increased the PSA gene expression and cell growth. These DHT effects were significantly attenuated by the addition of 17alpha-estradiol, 17beta-estradiol, or cyproterone acetate in a dose-dependent manner. These results indicate that estrogens produce an ER-isoform- and ER-ligand-specific modulation of DHT induction of PSA gene expression and prostate tumor cell growth, providing a molecular basis for designing favorable agents for the prevention and control of prostate cancer.

17alpha-estradiol inhibits LAPC-4 prostatic tumor cell proliferation in cell cultures and tumor growth in xenograft animals.

BACKGROUND: Blockade of androgen activity is a major effective therapy for advanced prostate cancer. Estrogen analogs have been used for prostate cancer therapy for years presumably by inhibiting testosterone biosyntheses, but with considerable adverse events due to their classic estrogenic activity. With the discovery of the estrogen receptor (ER) beta and its presence in prostate tumor cells, evaluation of estrogen analogs with less classic estrogenic activity in prostate cancer therapy is emerging. METHODS: The effects of 17alpha-estradiol (alphaE2), a stereo-isomer of 17beta-estradiol (betaE2), on dihydrotestosterone (DHT)-induced cell growth and gene expressions were examined in androgen-dependent LAPC-4 prostatic tumor cells and in LAPC-4 xenograft animals, and compared to those of betaE2. RESULTS: Both alphaE2 and betaE2 attenuated DHT induction of PSA gene expression, cell proliferation, and cell growth in cultured LAPC-4 cells. The inhibition of cell proliferation was associated with a blockade of DHT-induced cyclin A and cyclin D1 expression by alphaE2 and betaE2. In LAPC-4 xenograft mice, alphaE2 significantly inhibited tumor growth without altering the plasma testosterone level, while betaE2 failed to inhibit tumor growth even though it significantly inhibited PSA gene expression. CONCLUSION: alphaE2 is an effective agent for inhibition of DHT-induced PSA, cyclin A, cyclin D1 gene expression, and cell proliferation in LAPC-4 cells, and tumor growth in LAPC-4 xenograft mice.

[Study on the application and evaluation of methods for gene and antigen detection in plague surveillance program].

OBJECTIVE: To apply and evaluate new methods regarding specific gene and antigen detection in plague surveillance program. METHODS: 1798 samples from natural foci of plague were tested, using internal quality control multiple-polymerase chain reaction, F1 antigen marked by immuno chromatographic assay and enzyme linked immunosorbent assay. Culture of Yersinia pestis and reverse indirect hemagglutination assay were used as reference diagnostic methods. RESULTS: The overall positive rate of culture on Yersinia pestis together with gene and antigen detection was 7.34%, showing an 16.81% increase when comparing to 6.28% using Yersinia pestis culture method alone. The rate of coincidence was 97.13%. CONCLUSION: The new standard being used for specific gene and antigen detection could increase the positive rate of diagnosis on plague.

[Use of variable-number tandem repeats to examine genetic diversity of Bacillus anthracis].

OBJECTIVE: To study the genotyping of Bacillus anthracis based on multiple-locus variable-number tandem repeats(VNTR) in the B. anthracis genome. METHODS: We selected 13 VNTR loci (which cited from published articles) to study 88 strains of B. anthracis isolated from China. The methods used were: (1) Selecting the primers which were at both ends of the tandem repeat locus; (2) Amplifying the sequence of the locus by PCR; (3)cDetecting the PCR products by agarose gel and polyacrylamide electrophoresis; (4)Analyzing the PCR products and computing the molecular weight by analysis software of gel images;(5) Double-checking with sequencing results; (6)Reckoning the repeat numbers and study the VNTRs loci characters. RESULTS: (1) We used multiple-locus variable-number tandem repeat analysis (MLVA) to characterize 88 B. anthracis isolates from diverse geographic locations which were divided into 45 MLVA genotypes and 3 groups through cluster analysis. The genotypes was relative to restricted geographical region. It seemed clear that the multiple isolates from the same anthrax outbreak frequently having identical genotypes. (2)Results from VNTR analysis showed that A16R vaccine strain isolated from China was having the nature of representativeness in the country. CONCLUSION: Analysis showed that the VNTR patterns was an appropriate study method for B. anthracis genetic diversity from different geographical areas and different time. Isolates from the same anthrax outbreak had identical

[Establishment and application of real-time fluorescence polymerase chain reaction based on the TaqMan probes for detection of Yersinia pestis].

OBJECTIVE: Establishing and developing methods for quick, special and of Yersinia pestis (Y. pestis). METHODS: Using real-time fluorescence polymerase chain reaction (PCR) based on TaqMan technology with UDG anti-contamination systems and ROX reference dye, we established a method to detect Y. pestis. Probes and primers from pla, caf1, hms and inv gene were designed. An internal positive control was added to the reaction mixture in order to detect the presence of PCR inhibitors that were often found in biological samples. Sensitivity was evaluated by serial dilution of colons, internal template and Y. pestis strains while specificity was confirmed by amplifying real DNAs from bacteria, the representative Y. pestis strains and blind assay. RESULTS: The methods used could provide quick, special and sensitive detection of Y. pestis, with sensitivities of pla, f1, hms as 10, 1 and 1 copie(s) respectively. CONCLUSION: The newly developed technologies seemed to be well suited to identify the Y. pestis in case of emergency, bio-terrorist attack and surveillance of the epidemics.

[Study on the internal control on polymerase chain reaction in Yersinia pestis detection].

OBJECTIVE: For the detection of Yersinia pestis by polymerase chain reaction (PCR), internal control (IC) is required in order to prevent false negative results that might be caused by PCR inhibitors. METHODS: F1 antigen was amplified by PCR with primer F1 and the PCR product of primer F1 were cloned with TOPO TA cloning Kit. The plasmid of positive clone was then digested with HpaI. The digested plasmid and the PCR products of 16S rRNA were ligated with T(4) DNA ligase before the ligated products were transformed. Isolate plasmid DNA on positive clone and its concentration were measured. Plasmid DNA on different concentration by PCR amplification with primer F1 was analyzed and the standard concentration of IC was determined. RESULTS: Constructing an IC by inserting a 16S rRNA amplicon to the original target DNA between the two primer F1 sites, the size was longer than the target DNA. The standard concentration of IC was determined. CONCLUSION: An optimal IC concentration to increase the reliability of the PCR assays might be used to prevent false negative results and appeared to be useful for detection of Yersinia pestis.

[Study on the relation between the absence of one IS100 in 102 kb pgm locus of Yersinia pestis and the stability of pigmentation phenotype].

OBJECTIVE: To study the relation between the absence of one IS100 in the 102 kb pgm locus of Yersinia pestis and the stability of pigmentation phenotype (pgm(+)). METHODS: We amplified the segment including IS100 in 102 kb pgm locus of Yersinia pestis that isolated from all ecotypes in China by polymerase chain reaction (PCR). There were 171 strains isolated from 18 ecotypes in this study. One strain was chosen to be cloned and sequenced. RESULTS: Besides the type of Microtus brandti, the types of East-North Tianshan, A and B of West-North Tianshan, Microtus Qinghai had one band with about 2560 bp. These strains lost one IS100 in 102 kb pgm locus of Yersinia pestis. Their pgm(+) phenotype was stable. Some strains of ecotypes from Qilian Mountain, Qinghai-Tibet Plateau, Gangdisi Mountain, West Yunnan Mountain had no bands in the PCR products. Negative strains would lose the whole 102 kb pgm locus. The others had one band with 4492 bp. These strains had two IS100 which flanked the 102 kb pgm locus but the pgm(+) phenotype was unstable. CONCLUSION: Yersinia pestis which had only one IS100 would flank the 102 kb pgm locus and had stable pgm(+) phenotype while the Yersinia pestis that having two IS100 flanked the 102 kb pgm locus would have unstable pgm(+) phenotype.

A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis.

INI1 (integrase interactor 1)/hSNF5 is a component of the mammalian SWI/SNF complex and a tumor suppressor mutated in malignant rhabdoid tumors (MRT). We have identified a nuclear export signal (NES) in the highly conserved repeat 2 domain of INI1 that is unmasked upon deletion of a downstream sequence. Mutation of conserved hydrophobic residues within the NES, as well as leptomycin B treatment abrogated the nuclear export. Full-length INI1 specifically associated with hCRM1/exportin1 in vivo and in vitro. A mutant INI1 [INI1(1-319) delG950] found in MRT lacking the 66 C-terminal amino acids mislocalized to the cytoplasm. Full-length INI1 but not the INI1(1-319 delG950) mutant caused flat cell formation and cell cycle arrest in cell lines derived from MRT. Disruption of the NES in the delG950 mutant caused nuclear localization of the protein and restored its ability to cause cell cycle arrest. These observations demonstrate that INI1 has a masked NES that mediates regulated hCRM1/exportin1-dependent nuclear export and we propose that mutations that cause deregulated nuclear export of the protein could lead to tumorigenesis.

[The 102 kb pigmentation (pgm) locus of Yersinia pestis isolated from Microtus brandti].

OBJECTIVE: To find out the differences between 102 kb pgm locus of Yersinia pestis isolated from Microtus brandti with of other types, and the characters of Yersinia pestis isolated from Microtus brandti caused by their makeup of the 102 kb pgm locus. METHODS: 102 kb pgm locus of Yersinia pestis isolated from Microtus brandti and Yersinia pestis isolated from Marmota himalayana were amplified by polymerase chain reation (PCR) with 25 pair of nested primers. The PCR products of one pair of primer were obviously different, and then cloned and sequenced. Sequences were searched against current protein and nucleotide databases, using BLAST. RESULTS: The 102 kb pgm locus of Yersinia pestis isolated from Microtus brandti was devoid one IS100. In addition, it had more copies than other types in the similar variable-number tandem repeat sequences. CONCLUSION: The 102 kb pgm locus of Yersinia pestis was different from that of other types. It had only one IS100 flanked it, which corresponded to the character that its pgm(+) phenotype was stable. Further study was needed to confirm the relationship between the diminution virulence of Yersinia pestis isolated from Microtus brandti and the loss of IS100 and other changes.