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Callosobruchus maculatus is one of the most competitive stored grain pests, which causes a great loss to agricultural economy. However, due to an inadequacy of high-quality reference genome, the molecular mechanisms for olfactory and hypoxic adaptations to stored environments are unknown and require to be revealed urgently, which will contribute to the detection and prevention of the invasive pests C. maculatus. Here, we presented a high-quality chromosome-level genome of C. maculatus based on Illumina, Nanopore and Hi-C sequencing data. The total size was 1.2 Gb, and 65.17% (797.47 Mb) of it was identified to be repeat sequences. Among assembled chromosomes, chromosome 10 was considered the X chromosome according to the evidence of reads coverage and homologous genes among species. The current version of high-quality genome provides preferable data resources for the adaptive evolution research of C. maculatus., (© 2024. The Author(s).)

Application of silicon-based anodes is significantly challenged by low initial Coulombic efficiency (ICE) and poor cyclability. Traditional pre-lithiation reagents often pose safety concerns due to their unstable chemical nature. Achieving a balance between water-stability and high ICE in prelithiated silicon is a critical issue. Here, we present a lithium-enriched silicon/graphite material with an ultra-high ICE of ≥110 % through a high-stable lithium pre-storage methodology. Lithium pre-storage prepared a nano-drilled graphite material with surficial lithium functional groups, which can form chemical bonds with adjacent silicon during high-temperature sintering. This results in an unexpected O-Li-Si interaction, leading to in situ pre-lithiation of silicon nanoparticles and providing high stability in air and water. Additionally, the lithium-enriched silicon/graphite materials impart a combination of high ICE, high specific capacity (620 mAh g -1 ), and long cycling stability (>400 cycles). This study opens up a promising avenue for highly air- and water-stable silicon anode prelithiation methods., (© 2024 Wiley-VCH GmbH.)

A limited understanding of microbial interactions and community assembly mechanisms in constructed wetlands (CWs), particularly with different substrates, has hampered the establishment of ecological connections between micro-level interactions and macro-level wetland performance. In this study, CWs with distinct substrates (zeolite, CW_A; manganese ore, CW_B) were constructed to investigate the nutrient removal efficiency, microbial interactions, metabolic mechanisms, and ecological assembly for treating rural sewage with a low carbon-to-nitrogen ratio. CW_B showed higher removal of ammonia nitrogen and total nitrogen by about 1.75-6.75 % and 3.42-5.18 %, respectively, compared to CW_A. Candidatus_Competibacter (denitrifying glycogen-accumulating bacteria) was the dominant microbial genus in CW_A, whereas unclassified_f_Blastocatellaceae (involved in carbon and nitrogen transformation) dominated in CW_B. The null model revealed that stochastic processes (drift) dominated community assembly in both CWs; however, deterministic selection accounted for a higher proportion in CW_B. Compared to those in CW_A, the interactions between microbes in CW_B were more complex, with more key microbes involved in carbon, nitrogen, and phosphorus conversion; the synergistic cooperation of functional bacteria facilitated simultaneous nitrification-denitrification. Manganese ores favour biofilm formation, increase the activity of the electron transport system, and enhance ammonia oxidation and nitrate reduction. These results elucidated the ecological patterns exhibited by microbes under different substrate conditions thereby contributing to our understanding of how substrates shape distinct microcosms in CW systems. This study provides valuable insights for guiding the future construction and management of CWs., 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. Published by Elsevier Ltd.)

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 μm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae -1 ⋅day -1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics., 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. Published by Elsevier Ltd.)

Objective: The present study aims to explore the influencing factors of the scientific fitness literacy of nurses and provide a strategic basis for literacy improvement., Methods: A questionnaire on the influencing factors of scientific fitness literacy of nurses was designed by the group conducting the present study; the questionnaire was based on the socioecology model and the questionnaire preparation method. The general data questionnaire and the questionnaire on the influencing factors of scientific fitness literacy of nurses were adopted to investigate nurses in tertiary hospitals in order to analyze and discuss the influencing factors of their scientific fitness literacy., Results: (1) The questionnaire on the influencing factors of the scientific fitness literacy of nurses comprised five dimensions and 36 items. The overall item-content validity index was 0.833-1.000, the scale-content validity index was 0.974, and the overall Cronbach's α coefficient was 0.955; (2) the results of the pairwise Pearson correlation analysis showed that all five dimensions were positively correlated with the scientific fitness literacy of nurses; and (3) the results of the multiple linear regression analysis revealed that five dimensions, as well as the existence of exercise habits in daily life, had a significant impact on the scientific fitness literacy of nurses (P < 0.001)., Conclusion: The factors influencing the scientific fitness literacy of nurses involved all levels of the socioecological system. The methods of improving the awareness of the scientific fitness of nurses and providing opportunities for scientific fitness activities via the hospital played a critical role in literacy improvement. However, the lack of professional guidance and an atmosphere promoting scientific fitness might hinder literacy improvement., (© 2024. The Author(s).)

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.

Background: As the most common female malignancy, the incidence and mortality of endometrial carcinoma (EC) continue to increase worldwide. The effects of traditional standard therapy are limited; thus, novel therapeutic strategies urgently need to be developed. We sought to provide prospective targeting insights into EC therapeutics by comprehensively examining and confirming the biological molecular characterization of EC genes., Methods: The molecular characterization of EC genes was integrated and analyzed using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) databases. The differentially expressed genes (DEGs) were identified, and the abnormal expression of some core cell-cycle proteins in the EC specimens was determined by examining and integrating the TCGA and GTEx data. The enriched signaling pathways involved in tumor progression were also examined., Results: Immunohistochemical staining data from the Human Protein Atlas database showed that the differential expression levels of the cyclin dependent kinase inhibitor 2A (CDKN2A) and tyrosine threonine kinase (TTK) molecules, and the high messenger ribonucleic acid (RNA) levels of CDKN2A and TTK were associated with a poor prognosis in EC patients. High TTK expression was also significantly correlated with the tumor progression associated signaling pathways, such as the cell-cycle, nucleolus, and RNA processing pathways. The inhibition of TTK expression by a TTK inhibitor (NTRC0066-0) significantly suppressed the proliferation of the EC cells and synergistically increased the sensitivity of the EN and AN3-CA EC cell lines., Conclusions: The findings suggest that the TTK inhibitor could be used in EC therapy. This study highlighted the potential predictive role of TTK molecules and showed that TTK molecules might serve as prospective targets for EC therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5783/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Cascade reaction systems, such as protein fusion and synthetic protein scaffold systems, can both spatially control the metabolic flux and boost the productivity of multistep enzymatic reactions. Despite many efforts to generate fusion proteins, this task remains challenging due to the limited expression of complex enzymes. Therefore, we developed a novel fusion system that bypasses the limited expression of complex enzymes via a post-translational linkage. Here, we report a split intein-mediated cascade system wherein orthogonal split inteins serve as adapters for protein ligation. A genetically programmable, self-assembled, and traceless split intein was utilized to generate a biocatalytic cascade to produce the ginsenoside compound K (CK) with various pharmacological activities, including anticarcinogenic, anti-inflammatory, and antidiabetic effects. We used two types of split inteins, consensus atypical (Cat) and Rma DnaB, to form a covalent scaffold with the three enzymes involved in the CK conversion pathway. The multienzymatic complex with a size greater than 240 kDa was successfully assembled in a soluble form and exhibited specific activity toward ginsenoside conversion. Furthermore, our split intein cascade system significantly increased the CK conversion rate and reduced the production time by more than 2-fold. Our multienzymatic cascade system that uses split inteins can be utilized as a platform for regulating multimeric bioconversion pathways and boosting the production of various high-value substances.

Objective: The present study aims to analyze the current situation of scientific fitness literacy in nurses and provide a basis for all-round strategies for its improvement., Methods: Nurses in tertiary hospitals were conveniently selected as subjects in order to investigate the current situation regarding the scientific fitness literacy of nurses. The selection process was completed via the demographics questionnaire and the adult scale of scientific fitness literacy in sports medicine integration. As the minimum sample size was 5-10 times the number of variables in the study of exploring influencing factors of related variables and using the equation , given 20% of invalid questionnaires, the sample size should be >600 persons. The methods used for statistical analysis were descriptive statistical analysis and the t -test., Results: The scientific fitness literacy score in nurses was 110.81 ± 25.04 (relative value: 69.7%); this consisted of 50.85 ± 11.19 (73.7%) for scientific fitness knowledge dimension, 25.99 ± 5.35 (78.8%) for scientific fitness attitude dimension, and 33.97 ± 13.59 (59.6%) for scientific fitness behavior and skill dimension. The results of the independent sample t -test and analysis of variance showed that the differences in gender, education level, position, exercise habits, and balanced diet in daily life among nurses (regarding scientific fitness literacy) were statistically significant ( P < 0.05)., Conclusion: Nurses generally have an above-average level of scientific fitness literacy; this is mainly due to their good cognition and attitude regarding scientific fitness. However, their scientific fitness behaviors and skills are greatly inadequate. They are especially weak in completing WHO's recommended amount of exercise, mastering the cores of sports skills, undergoing a professional assessment before exercise, and developing exercise plans., Competing Interests: The authors declare there is no conflict of interest in this work., (© 2022 Liu et al.)

With the acceleration of urbanization, the proportion of surface imperviousness is increasing continuously in cities, resulting in frequent waterlogging disasters. In this context, storm water management, based on the low-impact development (LID) concept, offers an effective measure for the management of urban storm waters. First, the storm water management model (SWMM) was built for a typical cold climate city (Changchun) in China. Next, the two-stage calibrated model was employed to explore the surface runoff and storm sewer control effects of four LID combination plans. Finally, these plans were put through a "cost-benefit" evaluation through an analytic hierarchy process. According to the results, after using four LID plans, the reduction rates of peak runoff exceeded 40% and the problem of overflow load of the storm sewage was significantly mitigated. The infiltration-oriented Plan I proved to be the optimal plan, with the lowest proportions of the overflow nodes and full-load pipe sections in each return period, as well as with maximum overall performance. This study offers technical and conformed methodological support to cold cities for the prevention and control of waterlogging disasters and recycling of rainwater resources., (Copyright © 2021. Published by Elsevier Inc.)

Bulk chemicals such as ethylene glycol (EG) can be industrially synthesized from either ethylene or syngas, but the latter undergoes a bottleneck reaction and requires high hydrogen pressures. We show that fullerene (exemplified by C 60 ) can act as an electron buffer for a copper-silica catalyst (Cu/SiO 2 ). Hydrogenation of dimethyl oxalate over a C 60 -Cu/SiO 2 catalyst at ambient pressure and temperatures of 180° to 190°C had an EG yield of up to 98 ± 1%. In a kilogram-scale reaction, no deactivation of the catalyst was seen after 1000 hours. This mild route for the final step toward EG can be combined with the already-industrialized ambient reaction from syngas to the intermediate of dimethyl oxalate.

A mixed natural preservative composed of ε-polylysine (ε-PL), chestnut 70% ethanol extract (NE), and cinnamon hydrothermal extract (CW), was investigated for the reduction of Staphylococcus aureus . The minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) of seven natural extracts were investigated against a cocktail of three strains of S. aureus (ATCC 25923, ATCC 33591, and ATCC 33594). Three important factors (ε-PL, NE, and CW) were selected by using the Plackett-Burman (PB) design for the response surface model ( P  < 0.001). Following a central composite design, S. aureus were treated with mixtures of natural preservatives that included ε-PL, NE, and CW. The MIC and MBC of ε-PL and the natural extracts and ranged from 1 to 16 mg/mL (R 2  = 0.9857). The mixed natural preservative presented a synergistic antibacterial effect, at the optimum point. These results suggest that mixed natural preservatives of ε-PL, NE, and CW can lower the economic cost of food processing., Competing Interests: Conflict of interest The authors confirm that they have no conflicts of interest., (© The Korean Society of Food Science and Technology 2022.)

In order to understand the effects of different patterns of prefabricated fractures and grain size compositions on the fracture characteristics, acoustic emission characteristics and mechanical properties of the rock masses. We conducted compression shear experiments on square rock masses with different modes of prefabricated fractures and different grain size compositions. The experimental results showed that five fracture patterns were produced in specimens with different fracture patterns. The first fracture specimen, the fourth fracture specimen and the fifth fracture specimen were all brittle fractures. The other four specimens were not brittle fractures. The fracture patterns, fracture processes and mechanical characteristics of the different fracture pattern rock masses were revealed. The lowest peak shear stresses were found in specimens consisting of two grain size ranges and the highest peak shear stresses were found in specimens consisting of three grain size ranges. The highest shear displacements corresponding to the peak shear stresses were found in the specimens consisting of three particle size ranges. The effect of different grain size compositions on the peak shear stress and its corresponding shear displacement of the rock mass was revealed. Specimens consisting of one grain size range produced significant fracture and acoustic emission prior to the peak shear stress. The acoustic emission was jumped after the main fracture was formed. The specimen consisting of two grain size ranges produced fractures and strong acoustic emission characteristics after the peak shear stress. Thereafter, fracture reappeared and the acoustic emission signature increased again. As the specimen entered the residual strength phase, the acoustic emission was jumpy. Specimens consisting of three grain size ranges were brittle fractures with weak acoustic emission characteristics after the main fracture has formed. The cumulative energy of shear acoustic emission was the highest for a rock mass consisting of three grain size ranges. The rock mass consisting of three grain size ranges was also the strongest and most difficult to fracture because the grains were more fully embedded in each other., (© 2022. The Author(s).)

Objective: This study aimed to explore and analyze the effect of acupuncture on improving the enteral nutrition level and gastrointestinal dynamics in patients who had suffered a severe stroke., Methods: A total of 122 patients who experienced a severe stroke who were treated in the intensive care unit of the Affiliated Hospital of Hebei University (China) between September 2021 and March 2022 were randomly divided into two groups as follows: 1) the observation group, the participants of which received acupuncture combined with early enteral nutrition (61 cases); 2) the control group, the participants of which received early enteral nutrition (61 cases). Following treatment, the hemoglobin, neutrophil count, blood glucose, albumin, pre-albumin, immediate postprandial antral area, antral contraction frequency (at 2 min), and antral motility index on days 1 and 7 of treatment were compared between the two groups., Results: The total clinical effective rate was 96.72% in the observation group and 77.05% in the control group. The curative effect comparison between the two groups after seven days of treatment showed a lower probability of gastrointestinal bleeding, faster recovery of gastrointestinal motility, and a higher level of nutrient absorption in the observation group. Serum albumin, pre-albumin, hemoglobin, total lymphocyte count, immediate postprandial maximum (max) and minimum (mix) area of the gastric antrum, antral contraction frequency (at 2 min), and antral motility index were higher in the observation group than in the control group (P < 0.05). The difference in blood glucose levels between the two groups was not statistically significant (P > 0.05)., Conclusion: Acupuncture improved the enteral nutrition status of patients who had suffered a severe stroke and promoted gastrointestinal motility. The combination of acupuncture and early enteral nutrition could reduce damage to the gastrointestinal mucosal barrier caused by stress, changes in metabolism, and improved gastrointestinal function., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Grain size composition, crack pattern, and crack length have a significant influence on the crack characteristics, mechanical characteristics, and acoustic emission characteristics of rock masses. In this paper, the crack characteristics, mechanical characteristics, and acoustic emission characteristics of rock masses with different grain size compositions, different crack patterns, and different crack lengths were investigated under uniaxial compression. The rock masses were made of rock-like materials. The crack initiation locations and crack propagation directions were different for a specimen comprised of one grain size range compared with specimens comprised of two or three grain size ranges. The specimens comprised of one and three grain size ranges crack progressively. The specimen comprised of two-grain size ranges brittle fracture. The highest peak axial load was found in the specimens comprised of one grain size range. The results showed that tensile wing crack, anti-tensile wing crack, transverse shear crack, compression induced tensile crack, and surface spalling were produced in specimens with different crack orientations. The rock mass with 2 cm long crack started to produce cracks from the tip of the crack extending to the top and bottom surface, soon forming through cracks. The rock was brittle fracture. The axial load reached the maximum and then fell rapidly. The acoustic emission energy reached a rapid maximum and then decreased rapidly. The rock mass with 3 cm long fissures started to produce cracks that only extended from the tip of the fissures to the top surface but not to the bottom surface. The rock mass was progressively fractured. The axial load was progressively decreasing. The acoustic emission energy also rose and fell rapidly several times as the rock mass was progressively fractured. Different rock crack lengths led to different crack processes and crack patterns, resulting in very different acoustic emission characteristics., (© 2021. The Author(s).)

Objective: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy., Methods: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted., Results: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period., Conclusion: HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883)., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The separation of isomeric compounds from a mixture is a recurring problem in chemistry and phytochemistry research. The purification of pharmacologically active ginsenoside Rb 3 from ginseng extracts is limited by the co-existence of its isomer Rb 2 . The aim of the present study was to develop an enzymatic elimination-combined purification method to obtain pure Rb 3 from a mixture of isomers., Methods: To isolate Rb 3 from the isomeric mixture, a simple enzymatic selective elimination method was used. A ginsenoside-transforming glycoside hydrolase (Bgp2) was employed to selectively hydrolyze Rb 2 into ginsenoside Rd. Ginsenoside Rb 3 was then efficiently separated from the mixture using a traditional chromatographic method., Results: Chromatographic purification of Rb 3 was achieved using this novel enzymatic elimination-combined method, with 58.6-times higher yield and 13.1% less time than those of the traditional chromatographic method, with a lower minimum column length for purification. The novelty of this study was the use of a recombinant glycosidase for the selective elimination of the isomer. The isolated ginsenoside Rb 3 can be used in further pharmaceutical studies., Conclusions: Herein, we demonstrated a novel enzymatic elimination-combined purification method for the chromatographic purification of ginsenoside Rb 3 . This method can also be applied to purify other isomeric glycoconjugates in mixtures., (© 2019 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: Ginsenosides, triterpene saponins of Panax species, are considered the main active ingredients responsible for various pharmacological activities. Herein, a new protopanaxatriol-type ginsenoside called "ginsenoside MT1" is described; it was accidentally found among the enzymatic conversion products of ginsenoside Re., Method: We analyzed the conversion mechanism and found that recombinant β-glucosidase (MT619) transglycosylated the outer rhamnopyranoside of Re at the C-6 position to glucopyranoside at C-20. The production of MT1 by trans-rhamnosylation was optimized and pure MT1 was obtained through various chromatographic processes., Results: The structure of MT1 was elucidated based on spectral data: (20S)-3β,6α,12β,20-tetrahydroxydammarene-20-O-[ α -L-rhamnopyranosyl(1→2)-β-D-glucopyranoside]. This dammarane-type triterpene saponin was confirmed as a novel compound., Conclusion: Based on the functions of ginsenosides with similar structures, we believe that this ginsenoside MT1 may have great potential in the development of nutraceutical, pharmaceutical or cosmeceutical products.

Ginsenosides are known to have various highly pharmacological activities, such as anti-cancer and anti-inflammatory effects. However, the search for the most effective ginsenosides against the pathogenesis of atopic dermatitis (AD) and the study of the effects of ginsenosides on specific cytokines involved in AD remain unclear. In this study, ginsenoside Rh2 was shown to exert the most effective anti-inflammatory action on thymic stromal lymphopoietin (TSLP) and interleukin 8 in tumor necrosis factor-alpha and polyinosinic: polycytidylic acid induced normal human keratinocytes by inhibiting proinflammatory cytokines at both protein and transcriptional levels. Concomitantly, Rh2 also efficiently alleviated 2,4-dinitrochlorobenzene-induced AD-like skin symptoms when applied topically, including suppression of immune cell infiltration, cytokine expression, and serum immunoglobulin E levels in NC/Nga mice. In line with the in vitro results, Rh2 inhibited TSLP levels in AD mice via regulation of an underlying mechanism involving the nuclear factor κB pathways. In addition, in regard to immune cells, we showed that Rh2 suppressed not only the expression of TSLP but the differentiation of naïve CD4+ T-cells into T helper type 2 cells and their effector function in vitro. Collectively, our results indicated that Rh2 might be considered as a good therapeutic candidate for the alternative treatment of AD., Competing Interests: The authors declare no conflict of interest.

All previously reported C 70 isomers have positive curvature and contain 12 pentagons in addition to hexagons. Herein, we report a new C 70 species with two negatively curved heptagon moieties and 14 pentagons. This unconventional heptafullerene[70] containing two symmetric heptagons, referred to as dihept-C 70 , grows in the carbon arc by a theoretically supported pathway in which the carbon cluster of a previously reported C 66 species undergoes successive C 2 insertion via a known heptafullerene[68] intermediate with low energy barriers. As identified by X-ray crystallography, the occurrence of heptagons facilitates a reduction in the angle of the π-orbital axis vector in the fused pentagons to stabilize dihept-C 70 . Chlorination at the intersection of a heptagon and two adjacent pentagons can greatly enlarge the HOMO-LUMO gap, which makes dihept-C 70 Cl 6 isolable by chromatography. The synthesis of dihept-C 70 Cl 6 offers precious clues with respect to the fullerene formation mechanism in the carbon-clustering process., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ginseng has been shown to produce a cognitive improvement effect. The key molecular components in ginseng that produce pharmacological effects are ginsenosides. Previous studies reported a memory improvement effect of a few major ginsenosides. However, the identity of specific minor ginsenosides mediating such function remains unknown. Here, we report that a minor ginsenoside F1 improves memory function in APPswe/PSEN1dE9 (APP/PS1) double-transgenic Alzheimer's disease (AD) model mice. After 8-wk oral administration of F1 jelly, we observed that spatial working memory, but not context-dependent fear memory, was restored in AD mice. To search for a possible underlying molecular and cellular mechanism, we investigated the effect of F1 on Aβ plaque. We observed F1 administration reduced the Aβ plaque area and density in the cortex, but not in the hippocampus of AD mice. Next, we tested for the effect of F1 on the expression level of key molecules involved in learning and memory. Results from Western blot assay revealed that an abnormally reduced level of a phosphorylated form of CREB in the hippocampus of AD mice was restored to a normal level by F1 administration. Moreover, in the same animals, BDNF level was augmented in the cortex. Our results, therefore, suggest that minor ginsenoside F1 constitutes a promising target to develop therapeutic agents for AD.

Use of recombinant glycosidases is a promising approach for the production of minor ginsenosides, e.g., Compound K (CK) and F 1 , which have potential applications in the food industry. However, application of these recombinant enzymes for food-grade preparation of minor ginsenosides are limited by the lack of suitable expression hosts and low productivity. In this study, Corynebacterium glutamicum ATCC13032, a GRAS strain that has been used extensively for the industrial-grade production of additives for foodstuffs, was employed to express a novel β-glucosidase (MT619) from Microbacterium testaceum ATCC 15829 with high ginsenoside-transforming activity. A cellulose-binding module was additionally fused to the N-terminus of MT619 for immobilization on cellulose, which is an abundant and safe material. Via one-step immobilization, the fusion protein in cell lysates was efficiently immobilized on regenerated amorphous cellulose at a high density (maximum 984 mg/g cellulose), increasing the enzyme concentration by 286-fold. The concentrated and immobilized enzyme showed strong conversion activities against protopanaxadiol- and protopanaxatriol-type ginsenosides for the production of CK and F 1 . Using gram-scale ginseng extracts as substrates, the immobilized enzyme produced 7.59 g/L CK and 9.42 g/L F 1 in 24 h. To the best of our knowledge, these are the highest reported product concentrations of CK and F 1 , and this is the first time that a recombinant enzyme has been immobilized on cellulose for the preparation of minor ginsenosides. This safe, convenient, and efficient production method could also be effectively exploited in the preparation of food-processing recombinant enzymes in the pharmaceutical, functional food, and cosmetics industries.

Carboncones, a special family of all-carbon allotropes, are predicted to have unique properties that distinguish them from fullerenes, carbon nanotubes, and graphenes. Owing to the absence of methods to synthesize atomically well-defined carboncones, however, experimental insight into the nature of pure carboncones has been inaccessible. Herein, we describe a facile synthesis of an atomically well-defined carboncone[1,2] (C 70 H 20 ) and its soluble penta-mesityl derivative. Identified by x-ray crystallography, the carbon skeleton is a carboncone with the largest possible apex angle. Much of the structural strain is overcome in the final step of converting the bowl-shaped precursor into the rigid carboncone under mild reaction conditions. This work provides a research opportunity for investigations of atomically precise single-layered carboncones having even higher cone walls and/or smaller apex angles.

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng , promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, but VEGF-induced angiogenesis is often accompanied by a vascular permeability response. Ginsenosides are triterpenoid saponins from the well-known medicinal plant, ginseng, and have been considered a candidate for modulating angiogenesis. Here, we systemically investigated the effects of 10 different ginsenosides on human umbilical vein endothelial cells and newly identified that two PPT-type ginsenosides, F1 and Rh1 induce the migration and proliferation of endothelial cells. Interestingly, RNA transcriptome analysis showed that gene regulation induced by VEGF in endothelial cells is distinct from that of ginsenoside F1 and Rh1. In addition, F1 and Rh1 significantly inhibited vascular leakage both in vitro and in vivo, which are induced by vascular endothelial growth factor. Furthermore, comparative transcriptome analysis revealed that these effects of F1 and Rh1 on vascular leakage restoration are mainly caused by changes in VEGF-mediated TNFα signaling via NFκB, particularly by the suppression of expression and transcriptional activity of NR4A1 by F1 and Rh1, even in the presence of VEGF. These findings demonstrate that ginsenosides F1 and Rh1 can be a promising herbal remedy for vessel normalization in ischemic disease and cancer and that NR4A1 is the key target.

The anthracycline antibiotic doxorubicin is commonly used antineoplastic drug in breast cancer treatment. Like most chemotherapy, doxorubicin does not selectively target tumorigenic cells with high proliferation rate and often causes serve side effects. In the present study, we demonstrated the cellular senescence and senescence associated secretory phenotype (SASP) of both breast tumor cell MDA-MB-231 and normal epithelial cell MCF-10A induced by clinical dose of doxorubicin (100 nM). Senescence was confirmed by flattened morphology, increased level of beta galactose, accumulating contents of lysosome and mitochondrial, and elevated expression of p16 and p21 proteins. Similarly, SASP was identified by highly secreted proteins IL-6, IL-8, GRO, GM-CSF, MCP-1, and MMP1 by antibody array assay. Reciprocal experiments, determined by cell proliferation and apoptosis assays and cell migration and cell invasion, indicated that SASP of MDA-MB-231 cell induces growth arrest of MCF-10A, whereas SASP of MCF-10A significantly stimulates the proliferation of MDA-MB-231. Interestingly, SASP from both cells powerfully promotes the cell migration and cell invasion of MDA-MB-231 cells. Treatment with the natural product ginsenoside Rh2 does not prevent cellular senescence or exert senolytic. However, SASP from senescent cells treated with Rh2 greatly attenuated the above-mentioned bystander effect. Altogether, Rh2 is a potential candidate to ameliorate this unwanted chemotherapy-induced senescence bystander effect.

Objective: To observe the therapeutic effect of acupuncture therapy in the treatment of dysphagia in apoplexy patients., Methods: A total of 104 patients with post-stroke dysphagia were randomized into a control (conventional swallowing rehabilitation training) group and an acupuncture group ( n ＝ 52 cases in each one). In the control group, the conventional swallowing rehabilitation training was conducted, twice daily, 6 times a week for 4 weeks. In the acupuncture group, deep needling of main acupoints Lianquan (CV23) and Yifeng (TE17), and conventional acupuncture of adjuvant acupoints as Fengchi (GB20) and Fengfu (GV16), Wangu (GB12), Lieque (LU7), Jinjin (EX-HN12), Yuye (EX-HN13), etc. as well as electroacupuncture stimulation (15－20 Hz, 5 mA, and duration of 30 min) of ipsilateral CV23-GV16, TE17-GB20, and bilateral Neidaying acupoints were conducted. The acupuncture treatment was given once daily, 6 times a week for consecutive 4 weeks. In addition, patients of the two groups also received routine symptomatic treatment with drugs for anti-platelet aggregation, nourishing cranial nerve, lowering blood pressure, controlling blood glucose, improving cerebral circulation, etc. Before and after the treatment, the standard swallowing assessment (SSA, 18－46 points) and Kubota water swallowing test (WST, 1－5 grades) were conducted to evaluate the patient's swallowing function. The comprehensive therapeutic effect was assessed in accordance with the SSA and Kubota WST, and adverse reactions were recorded., Results: After the treatment, the SSA score was considerably reduced in the two groups relevant to their own pre-treatment (both P <0.05), and was significantly lower in the acupuncture group than in the control group ( P <0.05). The Kubota WST grade was evidently increased in the number of patients with grade Ⅰ ( P <0.05) and reduced in the numbers of patients with grade Ⅲ－Ⅴ in both groups relevant to their own pre-treatment, and was more patients with grade Ⅰ in the acupuncture group than in the control group ( P <0.05). Outcomes of the comprehensive therapeutic effect indicated that of the two 52 cases in the control and acupuncture groups, 8 (15.38%) and 19 (36.53%) were cured, 7 (13.46%) and 15 (28.45%) had marked improvement, 17 (32.69%) and 12 (23.08%) were effective, and 20 (38.46%) and 6 (11.54%) failed in the treatment, with the effective rate being 61.54% and 88.46%, respectively. The total effective rate of the acupuncture group was significantly higher than that of the control group ( P <0.05). The adverse reactions such as regional hematoma (in 3 cases) and pain (in 2 cases) in the acupuncture group, and choking-coughing in the control group were seen, being 9.62% and 11.54% in the incidence rate, respectively., Conclusion: Deep needling of main acupoints Lianquan (CV23) and Yifeng (TE 17) in combination with conventional acupuncture of other acupoints is effective in improving local glossopharyngeal function in apoplexy patients with dysphagia, which is obviously superior to conventional swallowing rehabilitation training in the therapeutic effect and is applicable in clinical practice.

The unpredictability of the polyoxometalate (POM) coordination model and the diversity of organic ligands provide more possibilities for the exploration and fabrication of various novel POM-based materials. In this work, a series of POM-based lanthanide (Ln)-Schiff base nanoclusters, [Ln(H 2 O) 2 (DAPSC)] 2 [Ln(H 2 O) 3 (DAPSC)] 2 [(SiW 12 O 40 )] 3 ·15H 2 O (Ln = Sm, 1; Eu, 2; Tb, 3), have been successfully isolated by the reaction of classical Keggin POMs, a Ln 3+ ion, and a Schiff-base ligand [2,6-diacetylpyridine bis(semicarbazone), abbreviated as DAPSC]. Both the hindrance effect of the organic ligand and charge balance endow the cluster with fascinating structural features of discrete and linear arrangement. The title compounds with dimensions of ca. 4 × 1 × 1 nm 3 are first trimeric polyoxometalate-based nanosized compounds, constructed by saturated POM anions (SiW 12 O 40 4- , denoted as SiW 12 ). Moreover, the properties (stability, electrochemistry, third-order nonlinear optics, and magnetism) of the compounds have also been studied.

Polyoxovanadates (III) are important class of polyoxometalates in molecular magnetism field, and particularly the systems which contain vanadium(III) centers. To date, only very few highly reduced vanadium polynuclear complexes were reported, which remains a significant challenge to synthesize novel polyoxovanadates, owing to the characteristics of easily oxidized vanadium(III). Herein, two unprecedented petaloid chiral octanuclear polyoxovanadates, l- and d-[H 2 N(CH 3 ) 2 ] 12.5 (H 3 N(CH 2 ) 2 NH 3 )(H 3 O) 1.5 (V III μ 2 -OH) 8 (SO 4 ) 16 ·2H 2 O (L-, D-V 8 ), have been successfully obtained by solvothermal method without any chiral auxiliary. Both L- and D-V 8 compounds contain the motif eight-membered ring (Vμ 2 -O) 8 (SO 4 ) 16 constituted of three different chiral entangled loops with the V atoms as nodes. Bond valence calculation (BVC) analysis indicates that all the V ions existed in L, D-V 8 are +3 value. The magnetic behavior of compounds indicated ferromagnetic coupling between vanadium(III) ions. To our knowledge, it is the first chiral highly reduced polyoxovanadates that exhibit excellent ferromagnetism.

The hepatitis C virus (HCV) E2 412-423 linear epitope has been found to be highly conserved across multiple HCV genotypes. The antibodies against this epitope have broadly neutralizing activity. Considering the poor immunogenicity of the epitope in humans and significant diversity in the global distribution of HCV genotypes, the aim of this study was to construct an anti-HCV phage library by using a series of optimal strategies to screen novel broadly neutralizing antibodies from Chinese donors. mRNA was isolated from peripheral blood samples of 39 patients who were anti-HCV positive. A phage library was constructed by inserting a single-chain variable fragment (scFv) gene repertoire into the T7Select10-3b vector. A synthetic peptide representing the HCV E2 N-terminal 412-423 region was used as "bait" for bio-panning. The binding affinities of phage clones to the synthetic peptide were evaluated through peptide-ELISA. Two scFv clones (R3-19 and R4-85) showing the strongest binding affinities were selected. The complementarity-determining regions (CDRs) of these clones were aligned with those of other previously reported broadly neutralizing anti-HCV antibodies, and multiple conserved amino acid sites were found. The optimized procedures ensured that two novel scFv antibodies were isolated from a constructed phage library and showed specific binding to the poorly immunogenic HCV E2 412-423 linear epitope. Keywords: phage antibody library; hepatitis C virus; broadly neutralizing antibody; synthetic peptide.

Two POM-based lanthanide derivatives, namely {triaqua[2,6-diacetylpyridine bis(semicarbazone)-κ 5 O,N,N',N'',O']terbium(III)}-μ-oxido-[tricosa-μ 2 -oxido-dodecaoxido-μ 12 -phosphato-dodecamolybdenum(VI)] pentahydrate (1), [Tb(C 11 H 15 N 7 O 2 )(H 2 O) 3 ][PMo 12 O 40 ]·5H 2 O, and the dysprosium(III) analogue (2), have been isolated successfully by the reaction of Keggin-POM [PMo 12 O 40 ] 3- (abbreviated as PMo 12 ), the Ln 3+ ion and the Schiff base 2,6-diacetylpyridine bis(semicarbazone) (DAPSC) ligand under hydrothermal conditions. [Ln(DAPSC)(H 2 O) 3 ][PMo 12 O 40 ]·5H 2 O is a PMo 12 -supported cluster featuring a lanthanide-Schiff base complex [denoted Ln-L(Schiff base)]. Single-crystal X-ray diffraction analysis reveals that the Ln III ion is in a distorted tricapped trigonal prismatic arrangement, coordinated by six O atoms and three N atoms. Two O atoms and three N atoms are provided by one DAPSC ligand, while the additional O atoms originate from a PMo 12 cluster and three water molecules. Hydrogen-bonding interactions between adjacent clusters form an interesting three-dimensional supramolecular structure. The identities of 1 and 2 were characterized by IR spectroscopy, thermogravimetric analysis and powder X-ray diffraction. Interestingly, both compounds possess excellent two-photon absorption (TPA) responses to the third-order nonlinear optics (NLO) (2264 GM for 1 and 941 GM for 2), suggesting that they have potential applications in the field of nonlinear optics (NLO). To our knowledge, 1 and 2 are the first POM-based Ln-L(Schiff base) complexes showing excellent two-photon responses. Meanwhile, the electrochemical properties of both compounds were studied in detail.

Despite wide potential applications of Gd-clusters in magnetocaloric effect (MCE) owing to f 7 electron configuration of Gd(III), the structural improvement in order to enhance MCE remains difficult. A new approach of the situ hydrolysis of acetonitrile is reported, and the slow release of small ligand CH 3 COO - is realized in the design and synthesis of high-nuclearity lanthanide clusters. A large lanthanide-exclusive cluster complex, [Gd 60 (CO 3 ) 8 (CH 3 COO) 12 (μ 2 -OH) 24 (μ 3 -OH) 96 (H 2 O) 56 ](NO3) 15 Br 12 (dmp) 5 ·30CH 3 OH·20Hdmp (1-Gd 60 ), was isolated under solvothermal conditions. To the best our knowledge, cluster 1 possesses the high metal/ligand ratio (magnetic density) and the largest magnetic entropy change (- Δ S m max = 48.0 J kg -1 K -1 at 2 K for Δ H = 7 T) among previously reported high-nuclearity lanthanide clusters.

Three new nickel-cluster-substituted polyoxometalates (POMs), [Ni6(H2O)9(μ3-OH)3(HSiW9O34)]2·12H2O (1), [Ni(en)(H2O)3][Ni6(H2O)3(en)2L(μ3-OH)3(HSiW9O34)]2·9H2O (2) (en = ethylenediamine; L = C7H5O2 = benzoic acid) and [Ni6(L')6(CH3COO)(H2O)3(μ3-OH)3(HPW9O34)]2·9H2O (3) (L' = C5NH5 = pyridine) were successfully isolated under hydro-/solvothermal conditions. 1-3 were structurally characterized by single-crystal XRD, elemental analyses, PXRD, IR, and TGA. Compound 1 mainly consists of a pair of {Ni6SiW9} fragments and some water molecules. Interestingly, the whole structure can be regarded as the connection of {Ni6SiW9} and another unit rotated 180° through Ni-O-W bonds, forming a dimeric structure {Ni6SiW9}2. Compounds 2 and 3 also have an {Ni6XW9}2 (X = Si, P) dimer, but there is a big difference in the connection between {Ni6SiW9} units. On this basis, mono-dentate conjugated organic ligands (benzoic acid (L) and pyridine (L')) were successfully introduced. It is noteworthy that pyridine molecules were first integrated into {Ni6SiW9}-based clusters and 3 features the highest number of organic ligands (six pyridines per Ni6) in the reported {Ni6XW9}-based clusters. The introduction of organic ligands to compounds 2 and 3 can bring about better third-order nonlinear optical properties. Magnetic research indicated the existence of ferromagnetic interactions in 2-3.

Triazole, similarly to imidazole, makes a prominent contribution to the proton conductivity of porous materials. To investigate the effects of triazole-based ligands in polyoxovanadates (POVs) on proton conduction, we designed and synthesized two decavanadate-based POVs, [Zn 3 (C 2 H 4 N 4 ) 6 (H 2 O) 6 ](V 10 O 28 )·14H 2 O (1) and [Zn 3 (C 2 H 3 N 3 ) 8 (H 2 O) 4 ](V 10 O 28 )·8H 2 O (2) constructed from the ligands 3-amino-1,2,4-triazole and 1 H -1,2,4-triazole, respectively, via an aqueous solution evaporation method. Surprisingly, complex 1 obtained a superior proton conductivity of 1.24 × 10 -2 S cm -1 under 60 °C and 98% RH, which is much higher than that of complex 2. Furthermore, due to the contribution of the conjugate properties of the ligands to the third-order nonlinear optical (NLO) properties, we also studied its two-photon responses and achieved satisfactory results., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

By the anionic template strategy, we have, for the first time, succeeded in introducing SiO 4 4- into 3d-4f huge clusters, obtaining two novel nanosized clusters with interesting nanosized cores of [Ln 78 Ni 64(62) Si 6 ] (1, Ln = Gd; 2, Ln = Eu). To the best of our knowledge, they are the largest heterometallic clusters incorporated with Si-O tetrahedra. In addition, compound 1 shows a maximum magnetic entropy (-Δ S m ) of 40.63 J kg -1 K -1 at 3.0 K at 7 T.

Fullerenes with novel structures find numerous potential applications, particularly in the fields of biology and pharmaceutics. Among various fullerene derivatives, those exhibiting amphiphilic character and capable of self-assembly into vesicles are particularly interesting, being suitable for delayed drug release. Herein, we report the synthesis and self-assembly of biocompatible hollow nanovesicles with bilayer shells from amphiphilic functionalized fullerenes C 60 R 5 Cl (R=methyl ester of 4-aminobutyric/glutamic acid or phenylalanine). The thus prepared vesicles exhibit sizes of 80-135nm (depending on R) and can be used as delayed-release carriers of anti-cancer drugs such as 5-fluorouracil, cyclophosphamide, and cisplatin, with the time of 5-fluorouracil release from drug-containing vesicles exceeding that of non-encapsulated forms by a factor of three. We further reveal the effect of R on the loading amount and release rate/amount of vesicle-encapsulated drugs, demonstrating a potential pharmaceutical application of the prepared nanovesicles depending on the nature of R., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Naturally occurring ginsenoside F1 (20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol) is rare. Here, we produced gram-scale quantities of ginsenoside F1 from a crude protopanaxatriol saponin mixture comprised mainly of Re and Rg1 through enzyme-mediated biotransformation using recombinant β-glucosidase (BgpA) cloned from a soil bacterium, Terrabacter ginsenosidimutans Gsoil 3082 T . In a systematic step-by-step process, the concentrations of substrate, enzyme, and NaCl were determined for maximal production of F1. At an optimized NaCl concentration of 200 mM, the protopanaxatriol saponin mixture (25 mg/ml) was incubated with recombinant BgpA (20 mg/ml) for 3 days in a 2.4 L reaction. Following octadecylsilyl silica gel column chromatography, 9.6 g of F1 was obtained from 60 g of substrate mixture at 95% purity, as assessed by chromatography. These results represent the first report of gramscale F1 production via recombinant enzyme-mediated biotransformation.

Objective: To study the association between the AKAP12 promoter methylation and recurrence of hepatocellular carcinoma. Methods: A total of 142 primary liver cancer patients underwent surgery in department of Hepatobiliary surgery in Peking University Cancer Hospital from 2003 to 2009 were selected as subjects in the survey; with the inclusion criteria as hepatocellular carcinoma, no cancer cells were observed in the surgical margin(SM) samples. All patients had neither lymph nor distant metastasis at the time of surgery, and receiving complete follow-up data for at least 3 years. By the end of May 2014, a total of 75 patients had relapsed of whom 71 died and there were no lost. All samples were acquired from the frozen surgical tissues. Genomic DNA was extracted using phenol/chloroform method and performed bisulfite modification following with polymerase chain reaction (PCR). AKAP12 methylation in hepatoma and the corresponding SM samples from 142 patients was determined by denature high-performance liquid chromatography (DHPLC) and bisulfite clone sequencing. Kaplan-Meier and Cox proportion hazard regression model were used to identify the factors related to the survival time. Results: In 142 cases, 125 patients (88.0%) were male and 17 (12.0%) cases were female. The median age was 52.5 years, ranging from 34 years to 76 years. AKAP12 methylation-positive rate was significantly higher in hepatomas than SMs (54.9% vs. 10.2%, P< 0.001). Patients with AKAP12 methylation-positive had less risk of the recurrence ( HR= 0.62, 95% CI : 0.39-0.99); with tumor diameter more than 5 cm ( HR= 1.53, 95 %CI: 1.00-2.50),portal vein invasion( HR= 4.53, 95% CI: 2.69-7.64) increased the recurrence risk. Moreover, portal vein invasion had a higher risk of death ( HR= 2.98, 95% CI: 1.73-4.98). Conclusion: There was significant association between AKAP12 DNA methylation and low risk of recurrence and long progression-free survival of hepatocellular carcinoma patients.

Cobalt-based nanomaterials have been intensively explored as promising noble-metal-free oxygen evolution reaction (OER) electrocatalysts. Herein, we report phase-selective syntheses of novel hierarchical CoTe 2 and CoTe nanofleeces for efficient OER catalysts. The CoTe 2 nanofleeces exhibited excellent electrocatalytic activity and stablity for OER in alkaline media. The CoTe 2 catalyst exhibited superior OER activity compared to the CoTe catalyst, which is comparable to the state-of-the-art RuO 2 catalyst. Density functional theory calculations showed that the binding strength and lateral interaction of the reaction intermediates on CoTe 2 and CoTe are essential for determining the overpotential required under different conditions. This study provides valuable insights for the rational design of noble-metal-free OER catalysts with high performance and low cost by use of Co-based chalcogenides., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the clinical and cytogenetic characteristics of high-level mixed-lineage leukaemia (MLL) gene amplification in patients with acute myeloid leukemia (AML)., Methods: The clinical and cytogenetic data of 2 AML patients with high-level MLL amplification from January 2010 to August 2016 were analyzed retrospectively., Results: The two AML cases were in middle-aged population. They were diagnosed as FAB subtype M5b and M2a respectively. Both of them had complex karyotypes with the aberrations of chromosome 11. One case was confirmed as MLL-PTD involving exons 2-9 by RT-PCR and sequencing. The other case without MLL-PTD was further analyzed by CytoScan HD analysis. The CMA results showed partial gain of 11q accompanied with partial loss in 11q, deletion of regions in 3p, 3q, 4q, 5q, 7q, 8q, 10p, 10q, 12p and 18q, as well as gain of 4p., Conclusion: The co-existence of -5/5q-, -7/7q- and highly complex karyotype may accelerate the poor prognosis. Thus how those cytogenetic abnormalities influencing the disease prognosis need to be further explored.

Previous studies used to enumerate circulating tumor cells to predict prognosis and therapeutic effect of colorectal cancer. However, increasing studies have shown that only circulating tumor cells enumeration was not enough to reflect the heterogeneous condition of tumor. In this study, we classified different metastatic-potential circulating tumor cells from colorectal cancer patients and measured FAM172A expression in circulating tumor cells to improve accuracy of clinical diagnosis and treatment of colorectal cancer. Blood samples were collected from 45 primary colorectal cancer patients. Circulating tumor cells were enriched by blood filtration using isolation by size of epithelial tumor cells, and in situ hybridization with RNA method was used to identify and discriminate subgroups of circulating tumor cells. Afterwards, FAM172A expression in individual circulating tumor cells was measured. Three circulating tumor cell subgroups (epithelial/biophenotypic/mesenchymal circulating tumor cells) were identified using epithelial-mesenchymal transition markers. In our research, mesenchymal circulating tumor cells significantly increased along with tumor progression, development of distant metastasis, and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal circulating tumor cells was significantly higher than that in epithelial circulating tumor cells, which suggested that FAM172A may correlate with malignant degree of tumor. This hypothesis was further verified by FAM172A expression in mesenchymal circulating tumor cells, which was strictly related to tumor aggressiveness factors. Mesenchymal circulating tumor cells and FAM172A detection may predict highrisk stage II colorectal cancer. Our research proved that circulating tumor cells were feasible surrogate samples to detect gene expression and could serve as a predictive biomarker for tumor evaluation.

Minor ginsenosides, such as compound K, Rg₃( S ), which can be produced by deglycosylation of ginsenosides Rb₁, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb₁, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b) derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231) in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb₁. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries., Competing Interests: The authors declare no competing financial interest.

The ginsenoside Rh2, a pharmaceutically active component of ginseng, is known to have anticancer and antitumor effects. However, white ginseng and red ginseng have extremely low concentrations of Rh2 or Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3]. To enhance the production of food-grade ginsenoside Rh2, an edible enzymatic bioconversion technique was developed adopting GRAS host strains. A β-glucosidase (BglPm), which has ginsenoside conversion ability, was expressed in three GRAS host strains (Corynebacterium glutamicum, Saccharomyces cerevisiae and Lactococus lactis) by using a different vector system. Enzyme activity in these three GRAS hosts were 75.4%, 11.5%, and 9.3%, respectively, compared to that in the E. coli pGEX 4T-1 expression system. The highly expressed BglPm&#95;C in C. glutamicum can effectively transform the ginsenoside Rg3-Mix [20(S)-Rg3, 20(R)-Rg3, Rk1, Rg5] to Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2, Rh3] using a scaled-up biotransformation reaction, which was performed in a 10-L jar fermenter at pH 6.5/7.0 and 37°C for 24 h. To our knowledge, this is the first report in which 50 g of PPD-Mix (Rb1, Rb2, Rb3, Rc, and Rd) as a starting substrate was converted to ginsenoside Rg3-Mix by acid heat treatment and then 24.5-g Rh2-Mix was obtained by enzymatic transformation of Rg3-Mix through by BglPm&#95;C. Utilization of this enzymatic method adopting a GRAS host could be usefully exploited in the preparation of ginsenoside Rh2-Mix in cosmetics, functional food, and pharmaceutical industries, thereby replacing the E. coli expression system.