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Ethnopharmacological Relevance: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine., Aim of Study: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones., Materials and Methods: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis., Results: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways., Conclusion: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

P-stereogenic phosphorus compounds are essential across various fields, yet their synthesis via enantioselective P-C bond formation remains both challenging and underdeveloped. We report the first copper-catalyzed enantioselective hydrophosphorylation of alkynes, facilitated by a newly designed chiral 1,2-diamine ligand. Unlike previous methods that rely on kinetic resolution with less than 50 % conversion, our approach employs a distinct dynamic kinetic asymmetric transformation mechanism, achieving complete conversion of racemic starting materials. This reaction is compatible with a broad range of aromatic and aliphatic terminal alkynes, producing products with high yields (up to 95 %), exclusive cis selectivity, and exceptional regio- and enantioselectivity (>20 : 1 r.r. and up to 96 % ee). The resulting products were further transformed into a diverse array of enantioenriched P-stereogenic scaffolds. Preliminary mechanistic studies were conducted to elucidate the reaction details., (© 2024 Wiley-VCH GmbH.)

Toll-like receptor (TLR) 7, a transmembrane signal transduction receptor expressed on the surface of endosomes, has become an attractive target for antiviral and cancer immunotherapies. TLR7 can induce signal transduction by recognizing single-stranded RNA or its analogs, leading to the release of cytokines such as IL-6, IL-12, TNF-α and type-I IFN. Activation of TLR7 helps to enhance immunogenicity and immune memory by stimulating immune cells. Herein, we identified a novel selective TLR7 agonist, GY101, and determined its ability to activate TLR7. In summary, in vitro, compound GY101 significantly induced the secretion of IL-6, IL-12, TNF-α and IFN-γ in mouse splenic lymphocytes; in vivo, peritumoral injection of GY101 significantly suppressed colon cancer CT26, as well as poorly immunogenic B16-F10 and 4T1 cancer cell-derived tumor growth by activating the infiltration of lymphocytes and polarization of M2-like macrophages into M1-like macrophages. These results demonstrate that GY101, as a potent TLR7 agonist, holds great potential for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Transition-metal-catalyzed enantioselective P-C cross-coupling of secondary phosphine oxides (SPOs) is an attractive method for synthesizing P-stereogenic phosphorus compounds, but the development of such a dynamic kinetic asymmetric process remains a considerable challenge. Here we report an unprecedented highly enantioselective dynamic kinetic intermolecular P-C coupling of SPOs and aryl iodides catalyzed by copper complexes ligated by a finely modified chiral 1,2-diamine ligand. The reaction tolerates a wide range of SPOs and aryl iodides, affording P-stereogenic tertiary phosphine oxides (TPOs) in high yields and with good enantioselectivity (average 89.2 % ee). The resulting enantioenriched TPOs were transformed into structurally diverse P-chiral scaffolds, which are highly valuable as ligands and catalysts in asymmetric synthesis., (© 2023 Wiley-VCH GmbH.)

Frankincense (FRA), the oily resin consisting of essential oils, boswellic acids (BAs) and polysaccharides, has been used to improve the blood circulation and relieve pain against carbuncles. According to the theory of traditional Chinese medicine, vinegar processed frankincense (VPF) can increase the effects of promoting blood circulation and relieving pain. Existing studies have carried out much on BAs and essential oils. However, the comparative analysis of polysaccharides from FRA and VPF has not been reported. In this paper, two polysaccharides were isolated and purified from FRA and the other two were from VPF, and their structures and physicochemical properties were analyzed. The immunological and anticoagulatant activities of the four polysaccharides were tested in RAW 264.7 cell and Sprague-Dawley rats, respectively. The polysaccharides purified from VPF showed better immunological and anticoagulatant activities than those in FRA. Therefore, polysaccharides may be one of the active substances for the synergistic effect of VPF., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Baeyer-Villiger monooxygenases (BVMOs) are important biocatalysts for the enzymatic synthesis of chiral sulfoxides, including chiral sulfoxide-type proton pump inhibitors for the treatment of gastrointestinal diseases. However, native BVMOs are not yet suitable for practical application due to their unsatisfactory activity and thermostability. Although protein engineering approaches can help address these issues, few feasible high-throughput methods are available for the engineering of such enzymes. Herein, a colorimetric detection method to distinguish sulfoxides from sulfides and sulfones was developed for prazole sulfide monooxygenases. Directed evolution enabled by this method has identified a prazole sulfide monooxygenase CbBVMO variant with improved activity and thermostability that catalyzes the asymmetric oxidation of lansoprazole sulfide. A 71.3 % increase in conversion and 6 °C enhancement in the melting point were achieved compared with the wild-type enzyme. This new method is feasible for high-throughput screening of prazole sulfide monooxygenase variants with improved activity, thermostability, and/or substrate specificity., (© 2022 Wiley-VCH GmbH.)

Background: Though the survival benefit of primary tumor operation for patients with signet ring cell carcinoma of the stomach is known, the specific characteristics of those patients who would profit from the operation are yet to be determined. To this end, a predictive model was developed to identify the conjecture that the survival profit from primary tumor operation would only be obtained by patients., Method: The clinical data of the patients with signet ring cell carcinoma of the stomach were obtained from the Surveillance, Epidemiology, and End Results database, and then divided into operation and no-operation groups based on whether the patients underwent the primary tumor operation. To remove the confounding factors, propensity score matching was employed, and it was hypothesized that the patients who had been operated on and lived a longer life than the median cancer-specific survival time of those who hadn't must have profited from the surgery. To discuss the independent factors of cancer-specific survival time in the beneficial group and the non-beneficial group, the Cox model was used, and based on the various vital predictive factors, a nomogram was drawn using logistic regression., Result: The number of eligible patients was 12,484, with 43.9% (5483) of them having received surgery. After employing propensity score matching, the cancer-specific survival time of the operation group was found to be apparently longer (median: 21 vs. 5 months; p < 0.001) than the no-operation group. In the operation group, 4757 (86.7%) of the patients lived longer than five months (beneficial group). The six indexes (beneficial and non-beneficial group) included gender, age, Tumor Node Metastasis stage, histologic type, differentiation grade, and tumor position, and were used as predictors to draw the nomogram. The nomogram was used to divide the patients who had taken operations into two groups: the beneficial operation group and the non-beneficial operation group. The beneficial operation group, it was found, survived longer than the non-beneficial operation group (median cancer-specific survival time: 28 vs. 3 months, p < 0.001). Moreover, there was we could tell little difference in survival between the two groups (median cancer-specific survival time: 3 vs. 5 months)., Conclusions: The predictive model created to select suitable candidates for surgical treatment from patients with signet ring carcinoma of the stomach could be adopted to identify certain patients benefiting from the primary tumor operation., (© 2022. The Author(s).)

Ethnopharmacological Relevance: Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored., Aim of the Study: The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway., Materials and Methods: To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies., Results: A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism., Conclusion: Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment., Aim of the Study: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model., Materials and Methods: The main compounds in CBP extract were analyzed by UPLC, 1 H-NMR and 13 C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H 2 O 2 -treated SRA01/04 lens epithelial cells., Results: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H 2 O 2 -induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins., Conclusion: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Walnut kernel has the actions of removing meteorism, dissipating stagnation and removing blood stasis and is used after being defatted in TCM. Defatted walnut powder extract (DWPE) has the abilities of anti-oxidation and lowering lipid levels in vivo. However, the effects and the potential mechanisms of DWPE on NAFLD have not been explored., Aim of the Study: The study were to investigate the anti-NAFLD effect of DWPE in high fat diet-induced C57BL/6 mice and demonstrate that whether DWPE developed the effect on anti-NAFLD by remodeling the compositions and abundances of gut microbiota., Materials and Methods: The inhibitory effect of DWPE on the development of NAFLD was conducted on C57BL/6 mice with a high fat diet and the regulation effect of DWPE on gut microbiota was verified on pseudo-sterile mice with treatment of broad spectrum antibiotics., Results: The results showed that the oral administration of DWPE remarkably alleviated hepatic lipid accumulation by decreasing the levels of TG, TC, LDL, MDA and increasing HDL. Meanwhile, the expressions of NF-κB and MAPKs family proteins were reduced by DWPE compared with HFD group. Otherwise, the efficacy of anti-NAFLD of DWPE was significantly decreased after treatment of antibiotics, which indicated the key role of gut microbiota in the therapeutic process. Furthermore, sequencing of 16S rRNA gene revealed that DWPE could revert the decreased relative abundance of gut microbiota caused by the long term of a high fat diet. And the disordered microflora was remodeled by DWPE including the reduction of Erysipelotrichia, Firmicutes and Actinobacteria as well as the increment of Bacteroidetes, Clostridiales, Bacteroidales S24-7, Prevotellaceae and Bacteroides., Conclusion: Taken together, DWPE had a preventing effect on NAFLD, which might be associated with the regulation of gut microbiota., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Most glioblastomas (GBMs) achieve cellular immortality by acquiring a mutation in the telomerase reverse transcriptase ( TERT ) promoter. TERT promoter mutations create a binding site for a GA binding protein (GABP) transcription factor complex, whose assembly at the promoter is associated with TERT reactivation and telomere maintenance. Here, we demonstrate increased binding of a specific GABPB1L-isoform-containing complex to the mutant TERT promoter. Furthermore, we find that TERT promoter mutant GBM cells, unlike wild-type cells, exhibit a critical near-term dependence on GABPB1L for proliferation, notably also posttumor establishment in vivo. Up-regulation of the protein paralogue GABPB2, which is normally expressed at very low levels, can rescue this dependence. More importantly, when combined with frontline temozolomide (TMZ) chemotherapy, inducible GABPB1L knockdown and the associated TERT reduction led to an impaired DNA damage response that resulted in profoundly reduced growth of intracranial GBM tumors. Together, these findings provide insights into the mechanism of cancer-specific TERT regulation, uncover rapid effects of GABPB1L-mediated TERT suppression in GBM maintenance, and establish GABPB1L inhibition in combination with chemotherapy as a therapeutic strategy for TERT promoter mutant GBM., Competing Interests: Competing interest statement: The Regents of the University of California have patents issued and pending for CRISPR technologies on which J.A.D. is an inventor. C.F. is a co-founder of Mirimus, Inc. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics, Scribe Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Caribou Biosciences, Intellia Therapeutics, eFFECTOR Therapeutics, Scribe Therapeutics, Synthego, Metagenomi, Mammoth Biosciences, and Inari. J.A.D. is a Director at Johnson & Johnson and has sponsored research projects by Pfizer, Roche Biopharma, and Biogen. J.F.C. is a co-founder of Telo Therapeutics, Inc. and has ownership interests. The other authors declare no competing interests., (Copyright © 2021 the Author(s). Published by PNAS.)

Parkinson's disease (PD) is the most common movement disorder in the world, affecting 1-2 per 1,000 of the population. The main pathological changes of PD are damage of dopaminergic neurons in substantia nigra of the central nervous system and formation of Lewy bodies. These pathological changes also occur in the intestinal tract and are strongly associated with changes in intestinal flora. By reviewing the research progress in PD and its association with intestinal flora in recent years, this review expounded the mechanism of action between intestinal flora and PD as well as the transmission mode of α - synuclein in neurons. In clinical studies, β diversity of intestinal flora in PD patients was found to change significantly, with Lactobacillusaceae and Verrucomicrobiaceae being significantly increased and Lachnospiraceae and Prevotellaceae being significantly decreased. In addition, a longer PD course was associated with fewer bacteria and probiotics producing short chain fatty acids, but more pathogenic bacteria. Moreover, the motor symptoms of PD patients may be related to Enterobacteriaceae and bacteria. Most importantly, catechol-O-methyltransferase inhibitors and anticholinergic drugs could change the intestinal flora of PD patients and increase the harmful flora, whereas other anti-PD drugs such as levodopa, dopamine agonist, monoamine oxidase inhibitors, and amantadine did not have these effects. Probiotics, prebiotics, and synbiotics treatment had some potential values in improving the constipation of PD patients, promoting the growth of probiotics, and improving the level of intestinal inflammation. At present, there were only a few case studies and small sample studies which have found certain clinical efficacy of fecal microbiome transplants. Further studies are necessary to elaborate the relationship of PD with microbes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Liang, Yang, Ren, Xia, Cui, Li and Gao.)

Objective: To investigate the variation of genes associated with Usher syndrome type 1(USH1)in 136 Chinese deafness families from Henan province. Methods: The data of 136 deafness families tested by next-generation sequencing(NGS) which identified in the center of genetics and prenatal diagnosis of the First Affiliated Hospital of Zhengzhou University from November 2016 to December 2019 were analysized and the variation frequency of six genes related to Usher syndrome type 1( MYO7A , USH1C , CDH23 , PCDH15 , USH1G , CIB2 ) were summarized. Results: Five deafness families were detected nine pathogenic or likely pathogenic variations in two genes, accounting for 3.7% of all families. Among them, four families were caused by MYO7A variations and one family was caused by CDH23 variation. Meanwhile, seven variations of two genes were reported for the first time. They were c.313delG, c.5257dupA, c.5435A>T, c.5636G>C, c.5722T>G of MYO7A , and c.155&#95;166del, c.4802delA of CDH23 . The patients' vision of family 2 and family 3 had no obvious abnormality at present, but according to genetic diagnosis and walking dealy, they were considered to be USH1. Conclusions: MYO7A is the most common caustive gene associated with USH1 in Henan deafness patients, the application of next-generation sequencing technology can make USH1 patients diagnosed earlier before the visual symptoms appear.

AcCHMO, a cyclohexanone monooxygenase from Acinetobacter calcoaceticus, is a typical Type I Baeyer-Villiger monooxygenase (BVMO). We previously obtained the AcCHMO M6 mutant, which oxidizes omeprazole sulfide (OPS) to the chiral sulfoxide drug esomeprazole. To further improve the catalytic efficiency of the AcCHMO M6 mutant, a focused mutagenesis strategy was adopted at the intersections of the FAD-binding domain, NADPH-binding domain, and α-helical domain based on structural characteristics of AcCHMO. By using focused mutagenesis and subsequent global evolution two key residues (L55 and P497) at the intersections of the domains were identified. Mutant of L55Y improved catalytic efficiency significantly, whereas the P497S mutant alleviated substrate inhibition remarkably. AcCHMO M7 (L55Y/P497S) was obtained by combining the two mutations, which increased the specific activity from 18.5 (M6) to 108 U/g, and an increase in the K i of the substrate OPS from 34 to 265 μM. The results indicate that catalytic performance can be elevated by modification of the sensitive sites at the intersection of the domains of AcCHMO. The results also provided some insights for the engineering of other Type I BVMOs or other multidomain proteins., (© 2020 Wiley Periodicals LLC.)

Objective: To analyze the genetic and clinical characteristics of MYO15A variants associated non-syndromic autosomal recessive deafness3 (DFNB3). Methods: The hearing test and high-throughput sequencing data of 108 families with non-syndromic hearing loss, who visited the Center of Genetics and Prenatal Diagnosis in the First Affiliated Hospital of Zhengzhou University from November 2016 to February 2019, were retrospectively analyzed to investigate the characteristics of MYO15A variation. Results: Compound heterozygous MYO15A variations were detected in nine patients from eight families, accounting for 7.4% of all 108 families. The variants were c.5910+1G>A/c.9417&#95;9418insTA, c.4234T>G/c.8324G>T, c.3926A>T/c.5002delC, c.9690+1G>A/c.10257&#95;10259delCTT, c.8324G>T/c.10419&#95;10423delCAGCT, c.4519C>T/c.6454G>C, c.6177+1G>T/c.10257&#95;10259delCTT and c.5692C>T/c.7396-1G>A. All patients had severe to profound hearing loss. Among the 14 variations, 12 variations were located in the main structural domains, including 5 in motor domain, 3 in FERM domain, 3 in MyTH4 domain and 1 in IQ motif. The c.3926A>T, c.4234T>G, c.4519C>T, c.5002delC, c.6454G>C, c.8324G>T, c.9417&#95;9418insTA and c.10419&#95;10423delCAGCT had not been reported in the Human Gene Mutation Database up to February 2020. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), 6 reported variants and the first reported c.4519C>T, c.5002delC, c.9417&#95;9418insTA and c.10419&#95;10423delCAGCT were identified as pathogenic variants, while c.8324G>T was likely pathogenic variant, and c.3926A>T, c.4234T>G and c.6454G>C were variants of uncertain significance. Conclusions: The variations of MYO15A in patients with DFNB3 are mainly complex heterozygous. The clinical phenotypes are mostly severe to profound hearing loss, and the mutation loci are mainly in the motor, FERM and MyTH4 domains.

Objective: To explore potential therapeutic targets other than androgen-deprivation treatment for prostate cancer by screening the proteins induced by androgen at palmitoylation modification level in LNCaP cells., Methods: The LNCaP cells were treated with androgen (Methyltrienolone, R1881, 5 nmol/L) or dimethyl sulfoxide (DMSO) for 24 h, and then labeled with alkynyl palmitic acid Alk-C16 (100 μmol/L). After that, the cells were collected, lysed, the total protein was extracted, agarose beads labeled with azide (1 mmol/L) were added, and the click-chemistry reaction was carried out at room temperature for 1 h. The covalent bond formed by click-chemistry reaction of azide and alkynyl group was used to enrich the palmitoylated proteins on agarose beads. Label-free quantitation (LFQ) was used to compare the protein palmitoylation level of R1881 treated and untreated cells to screen the proteins induced by androgen at palmitoylation modification level., Results: In this experiment, 907 potential palmitoylated proteins (mascot score>2, P<0.05) were identified, among which 430 proteins had LFQ values not zero at least twice. Among the 430 proteins, the palmitoylation levels of 92 candidates were increased by androgen treatment, and their LFQ values were significantly upregulated (>1.5-fold, P<0.05) in ≥2 samples of androgen-treated vs. untreated LNCaP cells. We also used the software of cytoscape to classify the 92 proteins, and found that the known functional proteins of them could be divided into three categories: metabolism related, protein folding related and translation initiation related. Among them, metabolism related proteins included lipid metabolism (6), glucose metabolism (7) and respiratory electron transport chain (8), and a small amount of amino acid metabolism (2) and other metabolism related proteins (2). Notably, the ratio of LFQ of cytochrome b-c1 complex subunit 2 (UQCRC2) was significantly (>3-fold, P<0.05) higher in androgen-treated cells compared with untreated cells, indicating that the palmitoylation level of UQCRC2 was enhanced by androgen most significantly than that of others. The second was long-chain acyl CoA dehydrogenase (ACADVL) related to lipid metabolism and glucose 6-phosphate dehydrogenase (PGD) related to glucose metabolism, but the LFQ ratio of them was less than 3-fold., Conclusion: The research on palmitoylation mechanism of metabolism, especially the proteins related to respiratory electron transport chain, will provide a new guidance for the diagnosis and treatment of prostate cancer and the development of targeted drugs.

Objective: To identify the chaperone of polypyrimidine tractor-binding protein-associated splicing factor (PSF) in myeloid leukemia cells, and to explore the mechanism and redistributive pattern to cell surface of PSF in chemo-sensitive HL60 cells and resistant HL60/DOX cells., Methods: The eukaryotic expression vector of PSF was transfected with liposomes transiently, then flow cytometry was used to detect the expression level of PSF on the cell surface 24 h, 48 h and 72 h after vector transfections. We constructed a chimeric expression vector, streptavidin binding peptide (SBP)-PSF, meanwhile this vector was transfected and made SBP-PSF fusion protein overexpress. In addition, we used streptavidin magnetic beads to precipitate the cellular chaperonin of PSF and then identified its chaperonin by mass spectrometry (MS). Lentiviral vectors containing cytokeratin18 (K18) interference sequences were transfected into 293T cells to prepare lentivirus. HL60 and HL60/DOX cells were infected with lentivirus to obtain stable interfering K18 cell lines. Next, flow cytometry was used to test the membrane relocation level of PSF. Together, these methods confirmed the similar or different mechanisms of the PSF redistributing to membrane synergistically mediated by K18 in HL60 and HL60/DOX cells., Results: The expression of membrane relocated PSF was detected every day for three days (at the end of 24 h, 48 h and 72 h) after transient overexpression. The expressing rate of PSF on the cell surface was 22.4%±3.5%, 37.9%±6.0%, 58.3%±8.8%, respectively in sensitive HL60 cells, while that was 4.7%±0.5%, 3.9%±0.6%, 2.9%±0.6% , respectively in resistant HL60/DOX cells. The difference of expressing rate on each day was significant, P<0.01. We identified K18 detected by co-immunoprecipitation and mass spectrum assay which was the cellular chaperone of PSF. We found that K18 knockdown decreased the PSF expression level which redistributed on cell surface from 48.9%±5.4% to 6.2%±1.0% in sensitive HL60 cells, and from 9.11%±1.2% to 2.21%±0.51% in resistant HL60/DOX cells, respectively., Conclusion: K18 is the intracellular chaperonin of PSF. The interaction of PSF and K18 mediates its redistribution to cell membrane in sensitive cells. While in resistant cells, PSF failed to relocate at the cell surface and accumulated in cells, which mediated resistance to chemotherapeutics.

Objective: To detect potential mutations in two Chinese families affected with deafness, so as provide prenatal diagnosis for them. Methods: Two Chinese families affected with deafness were identified at the genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from March 2018 to December 2018.Mutation analyses were carried out by next generation sequencing (NGS),suspected mutations were verified by Sanger sequencing in the probands, unaffected relatives. Prenatal diagnosis for high-risk fetus were carried out through Sanger sequencing. Results: The proband of family 1 carried a c.432delA and a c.617-2&#95;617-1insTC mutation of the TMPRSS3 gene, the proband of family 2 carried a c.271C>T(p.R91X) and a c.147dupTmutation ofthe TMPRSS3 gene, both parents of the two probands were carriers of heterozygous variants. Conclusions: Mutations in the TMPRSS3 gene are the suspected cause of deafness in two families. Application of next generation sequencing technologies make gene diagnosis of deafness efficiently and accurately and the molecular findings increase our understanding of the function of TMPRSS3 gene and enrich the human gene mutation database. It is helpful for recurrent genetic counseling and prenatal diagnosis for these families.

Ethnopharmacological Relevance: Morning glory seed (MGS), has been widely used in treating constipation especially towards children. Clinically, people usually take fried MGS (MGSF) in formulas to reduce its side effect. However, the safety of MGSF other than MGS has yet to be explored., Objective: The study aimed to reveal the potential mechanisms of using MGSF instead of MGS basing on chemistry, pharmacodynamics and toxicology., Methods: The chemical compositions of the extracts of MGS and MGSF were compared using UPLC-Q-TOF/MS method. Simultaneously, to prove the availability and safety of MGSF, we investigated the laxative effect and subchronic toxicity of MGS and MGSF and addressed the mechanism of laxative effect of them., Results: In this study, less phenolic acids and more fatty acids were detected in MGSF compared with the compounds in MGS. Moreover, we found that MGS group had stronger laxative effect than MGSF group via downregulating the expression of AQP3 protein. As for subchronic toxicity test, the body weights of MGS group were lower than MGSF group. In serum biochemistry and histopathological examinations, MGS group could cause more serious toxicity in liver, kidney and colon than MGSF group with higher values of BUN, Cr, AST and ALP., Conclusion: Based on the findings in this study, MGSF with varied compounds contents could still keep the laxative effect while retain less subchronic toxicity, which emphasized the necessity of processing and provided an insight into the rational use of MGSF in clinical practice., Competing Interests: Declaration of competing interest Authors have no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To detect gene mutation sassociated with deafness in four Waardenburg syndrome (WS) type Ⅱ patients, and to explore the possible mechanism of molecular genetics. Methods: All patients with WS were identified at the genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2018.Clinical materials and peripheral blood were collected from patients and family members. The genes associated with deafness of the patients were tested by next generation sequencing(NGS). And suspected mutations were verified by Sanger sequencing. Results: All patients carried heterozygous mutations in SOX10, they were c.355&#95;356insTCAGGCAGCGC, c.1106&#95;1107insTGGGGCCCCCCACACTA, c.511T>C (p.Y171H), c.91&#95;100del. According to the guidelines for genetic variation of the Amercian College of Medical Genetics and Genomics (ACMG), three frameshift mutations were pathogenic mutations, one missense mutation was likely pathogenic mutation. Conclusion: Application of next generation sequencing technologies make gene diagnosis of Waardenburg syndrome efficiently and accurately.

Objective: To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD. Methods: Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance. Results: Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant ( P < 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant ( P < 0.05). NAFLD group ( P = 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower ( P < 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant ( P = 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower ( P < 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant ( P < 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels ( r < 0, P < 0.05), and positively correlated with high-density lipoprotein levels ( r > 0, P < 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha ( r = -0.211, P = 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels ( r > 0, P < 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level ( r = 0.245, P = 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels ( r > 0, P < 0.05). Megamonas was negatively correlated with high-density lipoprotein levels ( r = -0.231, P = 0.027). Conclusion: A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.

Objective: The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI)., Materials and Methods: Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1β, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2., Results: The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1β in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group., Conclusion: EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The ability to engineer natural proteins is pivotal to a future, pragmatic biology. CRISPR proteins have revolutionized genome modification, yet the CRISPR-Cas9 scaffold is not ideal for fusions or activation by cellular triggers. Here, we show that a topological rearrangement of Cas9 using circular permutation provides an advanced platform for RNA-guided genome modification and protection. Through systematic interrogation, we find that protein termini can be positioned adjacent to bound DNA, offering a straightforward mechanism for strategically fusing functional domains. Additionally, circular permutation enabled protease-sensing Cas9s (ProCas9s), a unique class of single-molecule effectors possessing programmable inputs and outputs. ProCas9s can sense a wide range of proteases, and we demonstrate that ProCas9 can orchestrate a cellular response to pathogen-associated protease activity. Together, these results provide a toolkit of safer and more efficient genome-modifying enzymes and molecular recorders for the advancement of precision genome engineering in research, agriculture, and biomedicine., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

With the development of molecular biological technology, the association between genes and diseases has drawn increasing attention of researchers; the endothelial nitric oxide synthase (eNOS) gene has been reported to be a candidate gene for cardiovascular disease (CHD). The present study aimed to investigate the association between a polymorphism of eNOS and the risk of CHD in young people (≤40 years old), in addition to the underlying mechanism. A total of 234 cases of CHD in young individuals were collected as the CHD group and 228 cases of healthy individuals as the control group. Peripheral blood was collected and the genotype of the eNOS G894T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism, the gene frequency was calculated and the distributions of genotype and allele frequency between the two groups were compared. Bioinformatics tools were employed to analyze the differences in the local protein structures of the eNOS G894T polymorphism and the biological mechanism was preliminary discussed. The results demonstrated that there were significant differences in the distribution of genotype frequency and allele frequency of the eNOS G894T gene polymorphism between the CHD group and control group (P<0.05). The risk of CHD in GT and TT genotypes were higher compared with the GG genotype (P<0.05). The G894T polymorphism led to Glu298Asp mutation of encoded protein, which is within the active site of eNOS, and partial structures of the protein were converted from random coil to α‑helix. In conclusion, the eNOS G894T gene polymorphism was associated with the occurrence and development of CHD in young people. The potential mechanism is that the G894T polymorphism leads to altered protein structure, which affects the function of eNOS in generating nitric oxide and cardiovascular diastole. The results of the present study suggested a potential target gene for the prevention and treatment of CHD in young people (≤40 years old).

Osteopontin (OPN) has been investigated in the field of tumor research for several years. However, the prognostic role of OPN overexpression in acute myeloid leukemia (AML) remains controversial. A meta-analysis of four studies, including a total of 492 patients, was performed to determine the association of OPN with overall survival (OS) in AML patients. The random-effects model of Der Simonian and Laird was used to synthesize data; hazard ratio (HR) with its 95% confidence interval (CI) was used as the effect size estimate. It was observed that serum-based OPN was inversely correlated with OS and the difference was statistically significant (HR=1.83; 95% CI: 1.43-2.35; P<0.001). Experimental findings indicate that OPN overexpression is associated with a poor prognosis in AML and may be of prognostic value for AML stage and metastasis.

Objective To evaluate the value of high-frequency ultrasound (HFUS) in diagnosing peripheral nerve compression in patients with rheumatoid arthritis (RA). Methods The upper limb nerves were evaluated by HFUS in 80 RA patients (RA group) and 60 non-RA patients (control group),then the incidence of peripheral nerve compression was recorded respectively. RA patients with/without neurological symptoms were compared in terms of age,disease course,Health Assessment Questionnaire Disability Index (HAQ-DI) score,and clinical disease activity index (CDAI). Results The incidence of upper limb nerve compression in RA group was significantly higher than that in control group(15.0% vs. 3.3%,P=0.046).The patients with nerve compression was older [(60.2±11.4)y vs.(49.2±7.9)y;t=2.343,P=0.039] and had longer disease course [(9.50±5.99) y vs. (5.88±3.87)y;t=2.639,P=0.023] and higher HAQ-DI score (1.58±0.75 vs.0.85±0.67;t=2.490,P=0.030). These two groups had no statistical differences in CDAI (14.50±11.68 vs.16.62±9.24;t=1.141,P=0.278).Conclusions Peripheral neuropathies are common extra-articular manifestations in RA patients. HFUS can be valuable in patients suspected of RA.

We examined a possible association between HLA-A and -B polymorphisms and susceptibility to Henoch-Schönlein purpura (HSP) in Han and Mongolian children in Inner Mongolia, through a case-control study. Two hundred and sixty-eight unrelated children were enrolled, including 56 Mongolian and 50 Han children with HSP, 66 healthy Mongolian and 96 healthy Han children as a control group. HLA-A and -B alleles were indentified by PCR-sequence-specific oligonucleotide analysis and were further analyzed by PCR-sequencing-based typing (SBT). Frequencies of HLA-A*11, HLA-B*15 in Mongolian patients and HLA-A*26, HLA-B*35, HLA-B*52 in Han patients were higher than those in the corresponding control group (P < 0.05), while frequencies of HLA-B*07 and -B*40 in Mongolian HSP patients were lower than those in the control group (P < 0.05). Further analysis using PCR-SBT showed that all HLA-A*11 were HLA-A*1101, and most HLA-B*15 were HLA-B*1501 in Mongolian HSP patients. All HLA-A*26 were HLA-A*2601 and HLA-B*35 were mostly HLA-B*3503 in Han patients. There were more Han patients with severe manifestations than Mongolian patients (P < 0.05). Frequencies of HLA-A*26, HLA-B*35 and HLA-B*52 in Han patients were higher than in Mongolian patients (P < 0.05). We conclude that HLA-A*11(*1101) and -B*15(*1501) are associated with susceptibility to HSP in Mongolian children and HLA-A*26(*2601), HLA-B*35(*3503) and HLA-B*52 are associated with susceptibility to HSP in Han children. HLA-B*07 and -B*40 may be protective genes in Mongolian children. The different frequencies of HLA-A and -B in Mongolian and Han children may be responsible for the different manifestations in these two ethnic groups.

A field experiment was conducted to investigate the effects of irrigation with treated wastewater on the nutrient distribution in cucumber and tomato plants and their fruit quality. Irrigation with treated wastewater promoted tomato growth significantly, but had definite inhibition effect on cucumber growth. After the irrigation with treated wastewater, the nitrogen in plants had the characteristics of upward translocation, potassium was easily to be accumulated in cucumber leaf but not accumulated in tomato root, and sodium was mostly accumulated in root but less enriched in leaf, not giving damage to the plants. No significant effects were observed on the distribution of calcium, magnesium, and chlorine in plants. Under the irrigation with treated wastewater, the overall quality of cucumber and tomato fruits was less affected. The nitrate concentration in cucumber and tomato fruits was increased by 5.3% and 32.9%, respectively, but still lower than the state food safety standard of China.

The canal-lining project in Hetao Irrigation District (HID) for water-saving irrigation has been implemented for many years. By using statistical method, ordinary Kriging, and software ArcGIS 9.0, this paper analyzed the spatiotemporal variation of groundwater table depth and salinity in HID in September, 2001 and 2009. In the meantime, the vegetation distribution on the both shores of the lining part and non-lining part of Yangjiahe channel was also investigated. After the many years implementation of the project, the water diversion amount in HID in 2009 was reduced to 44.5 x 10(8) m3. The region area of groundwater table with a depth of 2.5-3.0 m was increased from 1.2 x 10(4) hm2 in 2001 to 9.11 x 10(4) hm2 in 2009. The region area of groundwater table with a depth of 2.0-2.5 m in 2009 took 80% of the total area of HID. In the northwestern region of HID, the groundwater salinity had reduced from 5000-10000 mg x L(-1) to 3000-5000 mg x L(-1). In Wulate irrigation region, the areas of salt water belt and half-salt water belt were increasing. After the canal-lining of Yangjiahe channel, the plant species and diversity index on both shores reduced, and some herbaceous plants with shallow roots showed degradation signs. The implementation of the project and the reduction of water diversion for irrigation did not exert negative effects on the maintenance of water surface area of Wuliangsuhai Lake.

A simple sample preparation method was developed by using a centrifugal ultrafiltration (CF-UF) device with hollow fiber (HF) for the determination of cefaclor in plasma by HPLC. Samples were placed into a homemade device, which was consisted of a glass tube and a U-shaped hollow fiber. The filtrate was withdrawn from the hollow fiber into a syringe after centrifugation and 20 μL was directly injected into the HPLC for analysis. The HPLC method had a linear calibration curve in the concentration range of 6.00×10(-2)-30.7 μg mL(-1)(r=0.9996). The limit of detection (LOD) and limit of quantitation (LOQ) were 0.02 and 0.06 μg mL(-1), respectively. The intra and inter-day precisions (RSD) were 1.7%, 1.2%, 1.0% and 3.6%, 2.5%, 1.9%, respectively, for three concentrations. Assay accuracy was higher than 99.2% and the absolute recovery was 86.8-92.5%. It is feasible to use this novel and low cost device for sample pretreatment for the analysis of cefaclor in plasma., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.

Objective: To study the expression of transcriptional factors T-bet and GATA3 mRNA and the levels of IFN-gamma and IL-4 in blood in children with acute idiopathic thrombocytopenic purpura (ITP) and investigate the tendency of polarization of Th1/Th2 in children with ITP., Methods: Blood T-bet and GATA3 mRNA expression were examined using RT-PCR and plasma IFN-gamma and IL-4 levels were measured using EIASA in children with acute ITP in acute (n=30) and remission stages (n=28). Twenty healthy children served as the controls., Results: Blood T-bet mRNA expression and IFN-gamma levels in children with ITP in the acute stage were markedly higher than those in the remission stage and controls (p<0.01). In contrast, blood GATA3 mRNA expression and IL-4 levels in children with ITP in the acute stage were significantly lower than those in the remmission stage and controls (p<0.01)., Conclusions: The high expression of T-bet and IFN-gamma and the low expression of GATA3 and IL-4 indicate the existence of Th1 polarization in children with acute ITP. This might be related to the regulation of T-bet and GATA3.

A new series of potential DNA bisintercalators have been designed by linking 8-hydroxy-quinoline to the 6-CH(2)OH group of glucose and connecting the 1-OH group of glucose with various linkers, such as quinol, glycol, and triethylene glycol. These new compounds were well-synthesized and fully characterized. Preliminary binding assays of these compounds to calf thymus DNA (CT-DNA) were conducted using UV-absorption and fluorescence spectroscopy analysis. The primary antitumor activity of these compounds was also performed.

In this study, di-n-butyltin(IV) oxide was reacted with the amino glucose analog, cis-4-[N-(1',3',4',6'-tetra-O-benzoyl-2-deoxy-glucopyranosyl)imido]-4-oxo-2-butenoic acid (1a) and o-[N-(1',3',4',6'-tetra-O-benzoyl-2-deoxy-glucopyranosyl) carbamoyl] benzoic acid (2a) to give the complexes bis-{cis-4-[N-(1',3',4',6'-tetra-O-benzoyl-2-deoxy-glucopyranosyl)imido-4-oxo-2-butenoic acid]-di-n-butyltin} carboxylate (1) and bis-{o-[N-(1',3',4',6'-tetra-O-benzoyl-2-deoxy-glucopyranosyl) carbamoyl-benzoic acid]-di-n-butyltin}carboxylate (2). These two compounds were then characterized by IR, NMR and MS. In vitro tests showed that both compounds have high cytotoxicity in four tumor cell lines (P388, HL-60, A549 and BEL-7402). Clonogenic assays demonstrated that both compounds 1 and 2 have hematopoietic cell toxicity at 10(-6) M.

A new remediation method for petroleum-salt contaminated soil was proposed, in which wheat straw was applied to enhance salt leaching and meanwhile block salt upmovement along the soil capillary. It was shown that the existence of petroleum increased the surface hydrophobicity of soil and thus hindered the leaching process once the oil content was above 1.5% (mass fraction). The application of 5% (mass fraction) wheat straw into the soil increased the efficiency of salt leaching from 3% to 25%. The effectiveness of wheat straw layer in inhibiting the salt upmovement along the soil capillary was also proven. Field test of this method was carried out in an area of 6400 m2, in which wheat straw layer of 5 cm was distributed in the depth of 25 cm. After 50 days, 80% of the testing area showed a normal soil electronic conductivity (soil EC <5 mS x cm(-1)) in contrast to 17% before leaching process. The concentrations of Na+ and Cl- were decreased from 1642.5 mg x kg(-1) and 1 301.2 mg x kg(-1) to 499.3 mg x kg(-1) and 433.8 mg x kg(-1), respectively. The remediated land upon the implementation of wheat straw gave a 72% of the regular wheat production obtained from the normal farmland, while the control land without wheat straw gave 12%. These results demonstrated the effectiveness and the high potential of using wheat straw for the salt leaching in remediation of petroleum-salt contaminated soil.

A field study on the coupling effect of new drought-resistant agents FA Handilong (FA HDL) and Beijing Green Angel (BGA) on the photosynthetic characteristics of Euonymus japonicus showed that these two agents could all decrease the stomatal conductance (gs) and transpiration rate (Tr) , and increase the net photosynthesis rate (Pn) and Pn/Tr of E. japonicus leaves. The inhibitory effect of FA HDL on gs and Tr was more significant when BGA was not applied. FA HDL inhibited the Pn and Pn/Tr when applied with BGA, but stimulated them when BGA was not applied. Applying BGA could obviously shorten the action period of FA HDL on E. japonicus. The fact that BGA could influence the effect of FA HDL was attributed to the properties of BGA and the photosynthetic characteristics of E. japonicus. The appropriate concentration of FA HDL to the E. japonicus without BGA application was 2 g x L(-1), and FA HDL was not appropriate to the E. japonicus applied with BGA.

Four new complexes of Ni(II), Cu(II), Zn(II) and Co(III) with HL (HL= N,N'-di-beta-D-glucosylethylenediamine) have been synthesized in methanol solutions. The compositions of the complexes determined by elementary analysis are [Ni(HL)(H2O)2]2+ Cl2.CH3OH.2H2O, [Cu(HL)]2+ Cl2.CH3CH2OH.3H2O, [Zn(HL)]2+ Cl2.H2O and [Co(HL)(H2O)(OH)]2+ Cl2.CH3OH.2H2O respectively. They were also characterized by IR, UV and NMR spectra which show that complexes of Ni(II) and Co(III) have octahedral configuration, while complexes of Cu(II) and Zn(II) have tetralhedral configuration. The hydrolytic kinetics of p-Nitrophenyl picolinate(PNPP) catalyzed by these complexes in buffer solution was also studied spectrophotometrically.

Objective: To measure hip bone mineral density (BMD) on different femoral rotations and to identify the influence of femoral rotation during hip densitometry., Methods: Forty women were recruited at the out-department of orthopedic, with the average age of 60.7 years (45-85 years), the average height of 161.8 cm (150-175 cm), and the average weight of 67.4 kg (48-80 kg). BMD measurement of hip was done in neutral position (0 degrees), 15 degrees and 30 degrees of internal rotation under quality control of DXA machine. All the subjects were asked to get down scan table and reposition after each measuring in different rotation., Results: Hip BMD of proximal femur (femoral neck, Ward's area and trochanter region) have significant variations in measurement (P < 0.01) among neutral position, 15 degrees and 30 degrees of internal rotation. There were more BMD change at the cancellous region (Ward's triangle and trochanter region) than at cortical bone area (femoral neck region). Statistical analysis showed a significant positive correlation for hip BMD change between neutral degrees to 15 degrees of internal rotation and 15 degrees to 30 degrees of internal rotation. But no correlation between neutral degrees to 30 degrees of internal rotation for hip BMD change., Conclusions: Femoral rotation was shown to have a significant effect on hip BMD measurements. Cortical bone region of hip have a less BMD change than cancellous bone region. Proper positioning of the femur during scan can improve precision significantly.