bluuebunny/crossref_metadata_2025 huggingface dataset:
FACTORS INFLUENCING PREHARVEST FRUIT SPLITTING IN ELLENDALE (C. reticulata).
Authors: Rabe Etienne , van Rensburg Piet , van der Walt Hennie , Bower John
Published: October 2019

Preharvest fruit splitting (PFS) is a serious problem in Ellendales, especially in hot, humid climactical areas. In control unsprayed treatments PFS can vary from 14 to 30% of the final yield. Any treatment during the fullbloom (FE) period aimed at increasing fruit set (gibberellic acid (GA) sprays, girdling), increases PFS levels, ranging from 40 to 60% of the final yield. This relates to a significant shift (delay) in the normal fruit drop pattern as compared to untreated trees.

We have evaluated various approaches aimed at reducing PFS in Ellendales: potassium treatments, from 10 weeks pre-blossom to six weeks after full-bloom, however, increased PFS levels, possibly due to increasing the initial fruit set levels; flower thinning, both chemical and mechanical, marginally reduced PFS, without adversely affecting yield; post-November drop GA application, 2,4-D and girdling treatments, aimed at stimulation of rind growth (not quantified) increased yields significantly (P<0.05) without concurrent increases in PFS.

Cross pollinated trees, and resultant high seed content in the fruit, yielded fruit with thicker rinds, with little or no PFS. GA application at FE reduced fruit seed content and peel thickness and increased PFS.

Any treatment causing high initial fruit set increases PFS. Flower: flower and fruit: fruit competition should be reduced early during the fruit growth phase, without adversely affecting final yields.
PRIMING PETUNIA
Authors: Khademi M. , Koranski D. S. , Karlovich P. T.
Published: October 2019

NaCl, KNO3 (0.3, 0.4, 0.5M), KH2P O4 (0.4, 0.5, 0.6M), and PEG 8000 (320 to 370 g/L with the increment of 10g/L) were used for priming Petunia `Ultra White' seeds for three to six days. Seeds were germinated in a growth chamber at 25C. Germination was recorded for seven days and the number of acceptable seedlings (seedlings with open cotyledon and normal root) was counted on the day seven. KH2P O4 at 0.6M was the best salt treatment. Rate of germination was improved by salt priming but the number of acceptable seedlings was lower than the control. Addition of GA (5 ppm) to the salt treatment was not effective. More abnormal seedlings were observed when seeds were primed in aerated salt solutions than when primed in petri dishes. Aerated PEG at 325 g/L for three days and 365 g/L for six days gave the best results. Priming in PEG improved percent of germination, rate of germination, and number of acceptable seedling as compared to control. Primed seeds lost some of the advantages of priming during 24hr air drying (22C), however quality was maintained when dried at 10C. Drying primed seed in 80% R.H. was not effective.
NITROGEN RELATIONS IN A SWEET CORN/WHITE CLOVER LIVING MULCH CROPPING SYSTEM
Authors: Altier Lee S. , Wien H. Christian
Published: October 2019

In a two-year field experiment, sweet corn was intercropped with a perennial cover of white clover. The clover was suppressed after corn emergence by rototilling. The nitrogen exchange between the corn, clover, and soil was closely monitored. Soil sampling indicated the rate and amounts of mineralization of nitrogen from soil organic matter and clover. Fertilizer labelled with 15-N was used to assess contributions of nitrogen from the various sources.

Results from 1989 showed little nitrogen benefit to the corn from the clover. Content of 15-N in the corn indicated that non-fertilizer nitrogen uptake was similar in monocropped and intercropped corn treatments. Corn yields were correlated with the amount of nitrogen fertilizer applied.
QUANTITIES AND FORMS OF NITROGEN UPTAKE THROUGHOUT DEVELOPMENT IN CHRYSANTHEMUM.
Authors: King Joseph J. , Stimat Dennis P.
Published: October 2019

Changes in quantity and form of nitrogen used were evaluated during development of Dendranthema × grandiflora `Iridon', `Sequoia' and `Sequest' grown in hydroponic solutions containing 28 ppm NO 3- (as Ca(NO3)2) and 28 ppm NH4+ (as(NH4)2SO4). Four plants of each cultivar were harvested every ten days over ninety days. Data were collected on plant height, leaf number, flower bud diameter, and root and shoot dry weights. Nutrient solutions were changed every ten days and sampled at days 1, 5, and 10 of each cycle. Concentrations of NO3- and NH 4+ of nutrient solutions and dried plant tissues were determined by micro-Kjeldahl. Total tissue nitrogen was determined for `Sequoia' by macro-Kjeldahl. Depletion of nitrogen from solutions approximated a 1:1 ratio for NH4+:NO3- throughout the crop cycle (r = 0.96). Although the sample date × cultivar interaction was significant for both forms of nitrogen, overall patterns of nitrogen uptake were similar among cultivars. Nitrogen uptake expressed per gram of tissue dry weight was greatest in the first month of development. However, total nitrogen uptake was greatest from days 40 to 60. Developmental stages corresponding to this period are a cessation of new leaf development and flower bud diameters of approximately 1.0 cm. Nitrogen uptake decreased rapidly as flowers expanded. Correlations between morphological changes and nitrogen demands could maximize the efficiency of nitrogen applications.
VARIATION IN FRUIT QUALITY CHARACTERISTICS OF PRICKLY PEARS (OPUNTIA SPECIES)
Authors: Kuti Joseph O.
Published: October 2019

This paper presents the results from a two-year study on fruit quality characteristics of prickly pear accessions belonging to five Opuntia species (O. ficus-indica, O. hyptiacantha, O. inermis, O. linderheimeri and O. megacantha) from a germplasm collection at Texas A&I University. Fruit soluble solids, pH, titratable acidity and ascorbic acid contents were determined using standard procedures. Significant differences in fruit soluble solids and ascorbic acid contents were observed. Accessions belonging to O. ficus-indica consistently had the highest soluble solids (> 12%) and ascorbic contents (>24mg/100g) while accessions belonging to O. lindheimeri consistently had the lowest soluble solids (<8%) and ascorbic acid contents (< 10mg/100g). Fruit acidity was generally low (<0.19%) for all the species. The results suggest potential for developing prickly pears for the fresh fruit market in south Texas.
BREEDING OF RHIPSALIDOPSIS AND SCHLUMBERGERA
Authors: Boyle Thomas H.
Published: October 2019

Rhipsalidopsis (Easter cactus) and Schlumbergera (Thanksgiving and Christmas cactus) are two genera of epiphytic cacti endemic to southeastern Brazil. Rhipsalidopsis is comprised of two species (R. gaertneri and R. rosea) and Schlumbergera contains five species (S. opuntioides, S. obtusangula, S. orssichiana, S. russelliana, and S. truncata). There is considerable potential for the improvement of commercial cultivars in both genera. Flower color and form, plant habit, postharvest performance, and the responsiveness to floral induction treatments are selection criteria used in breeding of Rhipsalidopsis. The selection criteria used in breeding of Schlumbergera are flower color and form, growth rate, phylloclade size and shape, plant habit, and the critical daylength for flowering. Inbreeding depression, self-incompatibility, and a long generation time (1.5 to 3 years) are impediments to breeding in both genera. Interspecific hybridization has been performed in Rhipsalidopsis and Schlumbergera, and significant phenotypic variation has been observed within interspecific hybrid populations.
Interseeding Snap Pea into Stands of Chile Pepper Reduces Yield of Pea More Than That of Chile
Authors: Guldan Steven J. , Martin Charles A. , Falk Constance L.
Published: October 2019

`Sugar Snap' snap peas (Pisum sativum L.) were interseeded into a stand of `Española Improved' chile pepper (Capsicum annuum L.) in July or Aug. in 1995, 1996, and 1997. Peas were interseeded as one or two rows per bed, giving planting rates of about 92 or 184 kg·ha-1, respectively. Our objectives were to determine: 1) if intercropped pea would reduce chile yield and vice versa; 2) the effects of pea planting rates and dates on pea yield. Intercropped peas reduced chile yield by about 22% in 1995, but had no significant effects in other years. Pea plants from the August intercrops reached the flowering stage but did not produce pods in 1995 or 1996; some small pods were produced from August intercrops in 1997. Final plant densities were lower and less uniform in 1996 than in 1995 or 1997. Intercropped peas yielded less than monocropped peas in all years. Pea yields ranged from 1370 to 3960 kg·ha-1 when monocropped, 31 kg·ha-1 (1996 single-row) to 646 kg·ha-1 (1995 double-row) when intercropped. In 1995 only, the double-row intercrop yielded more peas than the single-row intercrop. Pod yield/plant was reduced 80%, 98%, and 96% in 1995, 1996, and 1997, respectively, by intercropping. Estimated gross revenues for the treatments indicate that, under the price assumptions used in the study, interseeding snap peas into stands of chile in north-central New Mexico is not economically advantageous compared with monocropped chile.
Compósitos de quitosano-ácidos grasos reducen la infección de Botrytis cinerea en fresa en poscosecha
Authors: Sandoval Flores Ma. Guadalupe , Jiménez Mejía Rafael , Santoyo Gustavo , Alva Murillo Patricia Nayeli , López Meza Joel Edmundo , Loeza Lara Pedro Damián
Published: October 2019

Introducción: El moho gris es una de las principales causas de pudrición en poscosecha del fruto de fresa (Fragaria x ananassa Duch.), la cual es ocasionada por el hongo Botrytis cinerea Pers.:fr. El tratamiento con fungicidas químicos es el método principal de su control; no obstante, su uso ocasiona problemas de salud y contaminación. Lo anterior promueve la investigación hacia alternativas de control. El objetivo de la presente investigación fue evaluar el efecto de compósitos de quitosano-ácidos grasos sobre la infección de B. cinerea en frutos de fresa en poscosecha.Método: Se realizaron bioensayos in vitro para evaluar el efecto del quitosano, octanoato de sodio y ácido decanoico sobre el crecimiento micelial de B. cinerea. Asimismo, en bioensayos in vivo se evaluó la protección de los compuestos solos y en mezcla sobre la severidad de la infección del moho gris en frutos de fresa en poscosecha. Los tratamientos se evaluaron bajo un diseño completamente al azar, y los datos se analizaron mediante análisis de varianza (ANOVA) (p ≤ 0.05) y comparación de medias por el método de Tukey (p ≤ 0.05).Resultados: El quitosano inhibió el crecimiento en 100 % cuando se aplicó en concentraciones de 10, 12.5 y 15 mg/mL, mientras que el octanoato de sodio alcanzó el mismo porcentaje de inhibición en las concentraciones de 0.33 y 0.49 mg/mL. Finalmente, el ácido decanoico inhibió en 100 % a B. cinerea en las concentraciones de 0.17, 0.34 y 0.51 mg/mL. En los bioensayos in vivo, los mejores resultados de protección de los frutos de fresa de la infección por B. cinerea fueron aquellos en los que se utilizó el compósito quitosano/octanoato de sodio (12.5/0.49 y 15/0.49 mg/mL) con ausencia de severidad. También destacaron los tratamientos de quitosano (15 mg/mL), ácido decanoico (0.51 mg/mL) y del compósito quitosano/ácido decanoico (12.5/0.51 y 15/0.51 mg/mL), donde el grado de severidad fue entre 1 y 2.Discusión o Conclusión: El quitosano, octanoato de sodio y ácido decanoico inhibieron significativamente el crecimiento micelial in vitro de B. cinerea. El compósito quitosano/octanoato de sodio posee un efecto protector mayor de los frutos de fresa, en relación a los compuestos aplicados solos. El quitosano y el ácido decanoico presentaron un efecto protector significativo de los frutos, aplicados solos o como compósito. Lo anterior sugiere que estos compuestos podrían ser utilizados potencialmente en el control de B. cinerea en poscosecha.
Anthropogenic markers for source tracking of fecal contamination in Bayou Lafourche: a major drinking water source in Southeast Louisiana, USA
Authors: Martinez Stacy , Kilgen Marilyn , Corbin Angie , Nathaniel Rajkumar , Ramachandran Balaji , Boopathy Raj
Published: October 2019

Bayou Lafourche, which is the sole drinking water source for 300,000 people in Louisiana, has failed to consistently meet its designated use criteria set by the Louisiana Department of Environmental Quality (LDEQ). This resulted in a total maximum daily load to be imposed on the Bayou by the Environmental Protection Agency (EPA). These designated use water quality criteria include fecal coliform (FC) levels for drinking water source, primary contact recreation, and secondary contact recreation. The goal of this study was to identify and enumerate anthropogenic nonpoint source FC contamination from malfunctioning home sewage systems in the Bayou's watershed. Thirty-four sites along the Bayou were selected for the study. Samples were analyzed for optical brightener ratios, FC CFU/100 mL (mFC), Escherichia coli, and three human markers, including human polyomavirus BK, the Archaeon Methanobrevibacter smithii, and the human-associated Brevibacterioides HF 183 eubacteria. Frequencies of sites with all three anthropogenic molecular markers are considered positive for human fecal contamination. This study provided data to address the problem of malfunctioning on-site sewage systems in the Bayou Lafourche watershed.
Identifying the origins of extreme rainfall using storm track classification
Authors: Barnes Andrew Paul , Santos Marcus Suassuna , Garijo Carlos , Mediero Luis , Prosdocimi Ilaria , McCullen Nick , Kjeldsen Thomas Rodding
Published: October 2019

Identifying patterns in data relating to extreme rainfall is important for classifying and estimating rainfall and flood frequency distributions routinely used in civil engineering design and flood management. This study demonstrates the novel use of several self-organising map (SOM) models to extract the key moisture pathways for extreme rainfall events applied to example data in northern Spain. These models are trained using various subsets of a backwards trajectory data set generated for extreme rainfall events between 1967 and 2016. The results of our analysis show 69.2% of summer rainfall extremes rely on recirculatory moisture pathways concentrated on the Iberian Peninsula, whereas 57% of winter extremes rely on deep-Atlantic pathways to bring moisture from the ocean. These moisture pathways have also shown differences in rainfall magnitude, such as in the summer where peninsular pathways are 8% more likely to deliver the higher magnitude extremes than their Atlantic counterparts.
Removal of 4-chlorophenol from polluted water by aluminum–iron alloys
Authors: Wu Shangze , Tang Ka , Zhang Jingqi , Chen Xi , Hu Hanjun , Hu Qing , Yang Xiao Jin
Published: October 2019

Chlorophenols are extremely toxic to the environment and recalcitrant to biological degradation. Herein chemical degradation of 4-chlorophenol (4-CP) from aqueous solutions by zero-valent aluminum (Al), zero-valent iron (Fe), Al and Fe mixtures (Al/Fe mass ratio 90/10, labeled as Al/Fe10) and Al-Fe alloy (Al/Fe mass ratio 90/10, labeled as Al-Fe10) were investigated. No removal was found for 50 mg·L−1 4-CP under anoxic conditions at initial pH 2.5 during a period of 10 hrs while 56%, 83%, 78% and 99% of 4-CP were removed by Fe, Al, Al/Fe10 and Al-Fe10, respectively under aeration conditions. The removal of 4-CP by Al/Fe10 mixtures was primarily in the Fe mode in the beginning 4 h and then transitioned to the Al mode. The removal of 4-CP by Al-Fe10 alloy was accomplished via two intermediate products, hydroquinone (HQ) and 4-chlorocatechol (4-CC), and it was speculated that reactive oxygen species and hydroxyl radicals (·OH) play an important role in the degradation of 4-CP and that Al-Fe intermetallic compounds might catalyze the reactions. This study demonstrates that alloying Al with Fe offers a promising strategy for developing new materials for water and wastewater remediation.
Levels and distribution of progesterone in receiving waters and wastewaters of a growing urban area
Authors: Kasambala Hildegard R. , Rwiza Mwemezi J. , Mdegela Robinson H.
Published: October 2019

This study aimed at investigating the levels and distribution of progesterone in receiving waters and wastewaters in Arusha, a fast-growing urban area and the third largest city in Tanzania. Specifically, the study was conducted along the Themi River and the adjacent waste stabilization ponds (WSPs). Progesterone was detected and quantified by using an enzyme-linked immunosorbent assay (ELISA) kit. For Themi River samples, the level of progesterone obtained ranged from ‘no detection’ to 439 ng/L with a mean value of 120.3 ng/L. The levels detected were significantly higher in the midstream than the upstream and downstream sections of the river (P<0.05). The higher values at the midstream were attributable to livestock, WSPs and household effluents; agricultural activities; and sewage infiltration. Progesterone levels in the present study, although not extremely high, correspond to those associated with harmful effects in other studies. Results for samples collected from the WSPs indicated a release of 215 ng progesterone per L of the receiving waters. Although progesterone removal efficiency by the WSPs was 75%, the amount released was still high enough to cause harm to aquatic organisms. Thus, more efficient techniques are required to adequately remove progesterone to the recommended levels.
Subjetividade e produção de singularidades na formação docente
Authors: Brandão Elenilda Alves , Silveira Ederson Luís
Published: October 2019

PEREIRA, Marcos Villela. Estética da professoralidade: um estudo crítico sobre a formação do professor. 1. ed. Santa Maria: EdUFSM, 2013. 248p.
The role of forest vegetation in the mitigation of the ecological imbalances resulting from climate change in the Putna-Vrancea river basin
Authors: Costandache Cristinel , Dinca Lucian , Popovici Laurentiu , Tudor Ciprian
Published: October 2019

"Climatic changes displayed through extremes (thermic or hydric) correlated with uncontrolled anthropic interventions exercised over time on land usages are the main factors that emphasize ecological and hydric disequilibrium from the South, East part of Romania. Specific of our country, the torrential precipitation regime generates rapid floods in mountain and hill areas. Torrential and land degrading processes occur on slopes and on the main hydrographic network as a result of torrential runoffs. Their consequences extend on a larger area than the one on which they occur. This happens especially as a consequence of perturbing the hydrological regime of water courses, generating floods in downstream areas or the cogging of accumulation lakes in periods with rain redundancies.
Forest protection cultures (forest vegetation) installed on degraded or overexploited agricultural lands from the hill and mountain areas represent the most efficient solution for attenuating the negative effects of climatic changes. This happens by steadily re-establishing the hydrological equilibrium, together with creating an ecological equilibrium that has positive effects on the soil and waters.
This paper emphasized the results of investigations realized in 2017 concerning the characteristics of forest protection cultures created on strongly and excessively degraded lands, followed by their hydrological and anti-erosion effects in the context of extreme meteorological phenomenon. As such, the runoff coefficient had values lower than 6.5% (from the total volume of precipitations in 24 hours), while the specific erosion was under 0.24 t/ha/an. The maximum charge of alluvium (erosion) produced by rain is of over 40 mm; their frequency and intensity has increased lately."
Vegetable food waste for cotton dyeing-new directions for environmental sustainability
Authors: Bujdei Andreea , Gavrilas Simona , Dochia Mihaela , Munteanu Florentina Daniela
Published: October 2019

The present study considered the use of a by-product from winemaking for the treatment of wastewater from hemp retting process. To evaluate if different obtained extracts of grape marc (BRE-extract of refrigerated grape marc, BUE-extract of dried grape marc, BLE-extracted of lyophilised grape marc, BLM-ultrasound soaked lyophilised grape marc, BLM fUS-soaked lyophilised grape marc, no ultrasound treatment) are feasible to be used for the wastewater treatment. The chosen parameters (pH, turbidity, dissolved oxygen and conductivity) were monitored over 14 days and it was observed that starting with day 8 the measured values for all parameters remained constant.
Approaches concerning the conceptual model for the assessment of the natural fund values of the soil and water in natural protected zones
Authors: Stanescu Bogdan , Cuciureanu Adriana , Cernica Georgiana , Catrina Gina Alina
Published: October 2019

This article provides a detailed analysis of the fundamental elements required prior to conducting on-field research of an areas chosen as case studies for the assessment of soil and water quality in the unpolluted zones. The ultimate goal of the research to be carried out over the next two years is to obtain solid and reliable data on the quality of the two environmental components in these areas. All the data obtained will be integrated into a solid and georeference database, consisting of a sample identification module (soil and water) and a module of a varied parameters that will contain up to 42 parameters analyzed in the testing laboratories. Finally, the article presents the conclusions regarding the transposition of the proposed objectives into field and laboratory activities, graphical and descriptive details integrated into a conceptual model, universally valid in order to evaluate protected natural areas without direct anthropogenic impact. Particular importance in assessing these areas is attributed to detailing aspects that can influence the research results in major way. Issues related to the sampling and subsampling of soil and water samples, their conservation and transport to the laboratory are considered relevant and major. Geomorphological criteria of details, geographic and geological information are considered important in assessing the areas chosen as case studies. The five areas selected in the present study have been described and a number of objectives and activities have been proposed for on-site research to be carried out in the near future.
Biological monitoring used in assessment of the air pollutants
Authors: Cozea Andreea , Bucur Elena
Published: October 2019

Nowadays, the air pollution has become a major environmental problem due to rapid increase of industrialization and anthropogenic activities which led to climate change. Air pollution is considered as a harmful agent for human health. Different classes of pollutants like gaseous (SOx, NOx) are continuously released in air and perceived/recognized as pollutants. Among the biological models, plants could indicate pollution load in a particular area via alterations in physiological parameters so, there is a need for reliable and sustainable air pollution monitoring and control methods.
Structural model of forest ecosystem services’ payment for water quality improvement
Authors: Lybenova Mariyana , Chikalanov Alexandre , Petkov Yulian
Published: October 2019

The publication deals with the development of a structural model of payment schemes for ecosystem services (PES) oriented to usage of forests for water, soil and microclimate quality improvement. Proposed structural model is built on the Meta analyses base of more than 50 PES schemes worldwide. The proposed structural model has three top down levels – groups of categories, categories and attributes. There are seven groups of categories, 17 categories and more than 120 attributes. The structured information about studied PES schemes is stored in a warehouse managed by unique web platform created by the authors. An important part presented study is the developed generic use case of PES schemes with definition of seven participated actors.
The influence of emission sources on particulate matter pollution in adjacent areas
Authors: Danciulescu Valeriu , Pascu Luoana Florentina , Petrescu Mihaela , Cozea Andreea , Diodiu Raluca , Tanase Gheorghita , Pasca Maria
Published: October 2019

Particulates generated by anthropogenic activities are found in the ambient air in varying amounts, in a wide range of sizes and in a wide variety of chemical composition. The concentration of particulates at one site, as well as their composition, are influenced by their origin and dispersion factors. By chemical and dimensional analysis of particulates in an area, we can draw preliminary conclusions about the origin and level of pollution in that area. This paper presents the results obtained by concomitant monitoring of particulates emissions and the concentration of particulate matter in ambient air in the adjacent area of an industrial plant. The result of the measurements obtained and their correlation with the specific conditions during the monitoring period lead us to the conclusion that the concentration of particulate matter at the emission sources directly influences the concentrations of particulate matter in the neighbouring area.
Verifying compliance of a metallic surface treatment company with bat requirements, to minimize emissions of pollutants in water
Authors: Covacs Marius , Calamar Angelica Nicoleta , Toth Lorand , Simion Sorin , Simion Alexandru
Published: October 2019

The main activity of the studied company is treatment and coating of metals (galvanizing plating), trapping and treatment of waste water. Galvanizing consists in creating a superficial diffusion layer of iron alloy. BATs (Best Available Techniques) do not necessarily mean the most advanced technique available, but the best technique from an economic point of view for a particular installation. Results of the research relate to compliance of the industrial water treatment plant to BAT best available techniques, in order to minimize pollutants discharged into the sewerage network. Furthermore, the current paper identifies possible dysfunctional problems of the galvanizing plant and of the sewage treatment plant and makes suggestions of remedies for possible technical and organizational problems.
Turning Fear of Boron Toxicity into Boron-containing Drug Design
Authors: Soriano-Ursúa Marvin A. , Farfán-García Eunice D. , Geninatti-Crich Simonetta
Published: October 2019

Background:

Despite the historical employment of boron-containing compounds
(BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the
twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric
acid for specific purposes remains, and the discovery of natural BCCs with biological action
attractive for therapeutic purposes as well as the introduction of some new BCCs for
clinical use has reactivated the interest in studying the properties of these BCCs.

Methods:

We carried out a structured search of bibliographic databases for scientific peerreviewed
research literature regarding boron toxicity and linked that information to that of
BCCs in drug design and development. A deductive qualitative content analysis methodology
was applied to analyse the interventions and findings of the included studies using a theoretical
outline.

Results:

This review recapitulates the following on a timeline: the boron uses in medicine, the
data known about the toxicological profiles of some BCCs, the pharmacological properties of
some BCCs that are employed in cancer and infectious disease therapies, and the known
properties of BCCs recently introduced into clinical assays as well as the identification of
their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use
of new approaches taking advantage of some toxicological data to identify potent and efficient
BCCs for prevention and therapy while limiting their toxic effects.

Conclusion:

Data for boron toxicity can be strategically used for boron-containing drug design.
Drug Leads Derived from Japanese Marine Organisms
Authors: Uemura Daisuke , Kawazoe Yoshinori , Inuzuka Toshiyasu , Itakura Yuki , Kawamata Chiari , Abe Takahiro
Published: October 2019

Many natural products with extraordinary chemical structures and brilliant biological activities
have been obtained from marine organisms. We have investigated such fascinating bioactive
molecules, exemplified by the potent marine toxin palytoxin and the antitumor molecule halichondrin
B, which has been developed as the anticancer drug Halaven®, to explore novel frontiers in organic
chemistry and bioscience. Working within the traditional discipline, we have sought to acquire a
deeper understanding of biological phenomena. We introduce here our major work along with up-todate
topics. We isolated yoshinone A from marine cyanobacteria and completed a gram-scale synthesis.
Yoshinone A is a novel polyketide that inhibited the differentiation of 3T3-L1 cells into adipocytes
without significant cytotoxicity. The detailed mechanisms of action will be elucidated via further
experiments in vitro and in vivo. In this study, we explore the true producers of okadaic acid and
halichondrin B by immunostaining of Halichondria okadai with an antibody that was prepared using
these natural products as an antigen. We will analyze isolated symbionts and reveal biosynthetic
pathways.
Novel Antibacterial Strategies for Combating Bacterial Multidrug Resistance
Authors: Xu Xiao-Ling , Kang Xu-Qi , Qi Jing , Jin Fei-Yang , Liu Di , Du Yong-Zhong
Published: October 2019

Background:

Antibacterial multidrug resistance has emerged as one of the foremost global problems
affecting human health. The emergence of resistant infections with the increasing number of multidrug-resistant
pathogens has posed a serious problem, which required innovative collaborations across multiple disciplines to
address this issue.

Methods:

In this review, we will explain the mechanisms of bacterial multidrug resistance and discuss different
strategies for combating it, including combination therapy, the use of novel natural antibiotics, and the use of
nanotechnology in the development of efflux pump inhibitors.

Results:

While combination therapy will remain the mainstay of bacterial multi-drug resistance treatment,
nanotechnology will play critical roles in the development of novel treatments in the coming years.

Conclusion:

Nanotechnology provides an encouraging platform for the development of clinically relevant and
practical strategies to overcome drug resistance in the future.
Identification of the Active Constituents and Significant Pathways of Guizhi-Shaoyao-Zhimu Decoction for the Treatment of Diabetes Mellitus Based on Molecular Docking and Network Pharmacology
Authors: Zhang Qing , Li Ruolan , Peng Wei , Zhang Mengmeng , Liu Jia , Wei Shujun , Wang Jiaolong , Wu Chunjie , Gao Yongxiang , Pu Xufeng
Published: October 2019

Aim and Objective:

This study was designed to explore the active compounds and
significant pathways of Guizhi-Shaoyao-Zhimu decoction (GSZD) for treating diabetes mellitus using
molecular docking combined with network pharmacology.

Materials and Methods:

Chemical constituents of GSZD and diabetes-related target proteins were
collected from various databases. Then, compounds were filtered by Lipinski’s and Veber’s rules with
Discovery studio software. The “Libdock” module was used to carry out molecular docking, and
LibDockScores, default cutoff values for hydrogen bonds, and van der Waals interactions were
recorded. LibDockScore of the target protein and its prototype ligand was considered as the threshold,
and compounds with higher LibDockScores than the threshold were regarded as the active constituents
of GSZD. Cytoscape software was used to construct the herb-active molecule-target interaction
network of GSZD. ClueGO and CluePedia were applied to enrich the analysis of the biological
functions and pathways of GSZD.

Results:

A total of 275 potential active compounds with 57 possible pathways in GSZD were identified
by molecular docking combined with network pharmacology. TEN, INSR, PRKAA2, and GSK3B are
the four most important target proteins. Gancaonin E, 3'-(γ,γ-dimethylallyl)-kievitone, aurantiamide,
curcumin and 14-O-cinnamoylneoline, could interact with more than 14 of the selected target proteins.
Besides, 57 potential pathways of GSZD were identified, such as insulin signaling pathway,
metabolites and energy regulation, glucose metabolic process regulation, and positive regulation of
carbohydrate metabolic process, etc.

Conclusion:

These results showed that molecular docking combined with network pharmacology is a
feasible strategy for exploring bioactive compounds and mechanisms of Chinese medicines, and GSZD
can be used to effectively treat diabetes through multi-components and multi-targets & pathways.
Medicinal Chemistry of Multiple Sclerosis: Focus on Cladribine
Authors: Biernacki Tamás , Sandi Dániel , Bencsik Krisztina , Vécsei László
Published: October 2019

Background:

In the recent years, many novel Disease-Modifying Drugs (DMD) have been introduced to the market in the treatment of multiple sclerosis.

Objectives:

To provide the reader with an up to date, compact review on the pharmacokinetic properties, mechanism of action, and clinical attributes of one of the most recently approved drugs in the therapy of multiple sclerosis, cladribine.

Conclusion:

Cladribine tablets proved to be a highly efficient treatment choice for Relapsing- Remitting Multiple Sclerosis (RRMS), especially for patients with high disease activity. It is the first DMD for MS with a complex mechanism of action, by inhibiting the adenosine-deaminase enzyme it increases the intracellular levels of deoxyadenosine triphosphate, which with relative selectivity depletes both T- and B-cells lines simultaneously. However long term follow-up safety and effectiveness data are still missing, and clear treatment protocols are lacking beyond the first two treatment years cladribine should prove to be a valuable addition to the therapeutic palette of RRMS, and potentially for Clinically Isolated Syndrome (CIS) as well.
High Throughput Multiplex SNP-analysis in Chronic Obstructive Pulmonary Disease and Lung Cancer
Authors: Elek Zsuzsanna , Kovács Zsuzsanna , Keszler Gergely , Szabó Miklós , Csanky Eszter , Luo Jane , Guttman András , Rónai Zsolt
Published: October 2019

Background:

A number of human inflammatory diseases and tumors have
been shown to cause alterations in the glycosylation pattern of plasma proteins in a specific
manner. These highly variable and versatile post-translational modifications finetune
protein functions by influencing sorting, folding, enzyme activity and subcellular
localization. However, relatively little is known about regulatory factors of this procedure
and about the accurate causative connection between glycosylation and disease.

Objective:

The aim of the present study was to investigate whether certain single nucleotide
polymorphisms (SNPs) in genes encoding glycosyltransferases and glycosidases
could be associated with elevated risk for chronic obstructive pulmonary disease
(COPD) and lung adenocarcinoma.

Methods:

A total of 32 SNPs localized in genes related to N-glycosylation were selected
for the association analysis. Polymorphisms with putative biological functions (missense
or regulatory variants) were recruited. SNPs were genotyped by a TaqMan OpenArray
platform. A single base extension-based method in combination with capillary gel electrophoresis
was used for verification.

Results:

The TaqMan OpenArray approach provided accurate and reliable genotype
data (global call rate: 94.9%, accuracy: 99.6%). No significant discrepancy was detected
between the obtained and expected genotype frequency values (Hardy–Weinberg equilibrium)
in the healthy control sample group in case of any SNP confirming reliable sampling
and genotyping. Allele frequencies of the rs3944508 polymorphism localized in the
3’ UTR of the MGAT5 gene significantly differed between the sample groups compared.

Conclusion:

Our results suggest that the rs34944508 SNP might modulate the risk for
lung cancer by influencing the expression of MGAT5. This enzyme catalyzes the addition
of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of
biantennary N-linked oligosaccharides, thus, increasing branching that is the characteristic
of invasive malignancies.
The Present and Future of Novel Protein Degradation Technology
Authors: Xia Liwen , Liu Wei , Song Yinsen , Zhu Hailiang , Duan Yongtao
Published: October 2019

Proteolysis targeting chimeras (PROTACs), as a novel therapeutic modality, play a vital role
in drug discovery. Each PROTAC contains three key parts; a protein-of-interest (POI) ligand, a E3 ligase
ligand, and a linker. These bifunctional molecules could mediate the degradation of POIs by hijacking
the activity of E3 ubiquitin ligases for POI ubiquitination and subsequent degradation via the ubiquitin
proteasome system (UPS). With several advantages over other therapeutic strategies, PROTACs
have set off a new upsurge of drug discovery in recent years. ENDTAC, as the development of PROTACs
technology, is now receiving more attention. In this review, we aim to summarize the rapid progress
from 2018 to 2019 in protein degradation and analyze the challenges and future direction that need
to be addressed in order to efficiently develop potent protein degradation technology.
Pathophysiological Mechanisms Linking Type 2 Diabetes and Dementia: Review of Evidence from Clinical, Translational and Epidemiological Research
Authors: Bello-Chavolla Omar Yaxmehen , Antonio-Villa Neftali Eduardo , Vargas-Vázquez Arsenio , Ávila-Funes José Alberto , Aguilar-Salinas Carlos Alberto
Published: October 2019

Background:

Type 2 diabetes represents an increasing health burden world-wide and its prevalence in particularly higher in elderly population. Consistent epidemiological evidence suggests an increased risk of dementia associated to type 2 diabetes; the mechanisms underlying these associations, however, remain unclear.

Objective:

The study aims to review epidemiological, clinical and pre-clinical data that weigh on pathophysiological links, mechanisms of disease and associations between type 2 diabetes and dementia to identify areas of opportunity for future research.

Methods:

We searched the following electronic bibliographic databases: PUBMED, EMBASE, SCIELO, MEDLINE and OVID for clinical, translational and epidemiological research literature that summarize diabetes-related risk factors for dementia, metabolic and neurological changes associated to T2D, evidence of therapeutic approaches in type 2 diabetes and its pathophysiological implications for dementia.

Results:

Type 2 diabetes mellitus increases risk for all-cause dementia, vascular dementia and Alzheimer’s disease. The most evaluated mechanisms linking both disorders in pre-clinical studies include an increase in neuronal insulin resistance, impaired insulin signaling, pro-inflammatory state, mitochondrial dysfunction and vascular damage which increase deposition of β-amyloid, tau proteins and GSK3β, leading to an earlier onset of dementia in individuals with impairment in the glucose metabolism. Neuroimaging and neuropathology evidence linking cerebrovascular lesions, neurodegeneration and particularly small-vessel disease in the onset of dementia is consistent with the increased risk of incident dementia in type 2 diabetes, but consistent evidence of AD-related pathology is scarce. Epidemiological data shows increased risk of dementia related to hypoglycemic episodes, glycemic control, metabolic syndrome, insulin resistance and genetic predisposition, but the evidence is not consistent and statistical analysis might be affected by inconsistent covariate controlling. Therapeutic approaches for T2D have shown inconsistent result in relation to dementia prevention and delay of cognitive decline; lifestyle intervention, particularly physical activity, is a promising alternative to ameliorate the impact of disability and frailty on T2D-related dementia.

Conclusion:

Vascular disease, inflammation and impaired brain insulin signaling might occur in T2D and contribute to dementia risk. Evidence from epidemiological studies has not consistently reported associations that could integrate a unified mechanism of disease in humans. Evaluation of the effect of antidiabetic medications and non-pharmacological interventions in dementia prevention in type 2 diabetes is promising but has thus far offered inconsistent results.
The design, synthesis, pharmacokinetic and pharmacodynamic evaluation of acyloxyalkyl-substituted T705 prodrugs
Authors: Li Xingzhou , Zhang Tianhong , Zhong Wu
Published: October 2019

Background:

The pharmacokinetic properties of T705 are not optimal for the development of new drugs.

Objective:

To improve the pharmacokinetic properties of T-705, structure modification of T-705 was conducted using a prodrug strategy.

Method:

The acidic amide H atom (N4-H) of T705 was attempted to be replaced with acyloxyalkyl groups following the prodrugs development strategy for carboxylic acids, and the resulting compounds were investigated whether could work as prodrugs and contribute to improving the pharmacokinetic properties of the parent compound T705 in vivo.

Results:

4-acyloxyalkyl-T705 (4a–e), did act as prodrugs in vivo. 4-iso-butyryloxymethyl-T705 (4a) and 4-acetoxymethyl-T705 (4b) could significantly improve the plasma concentration and systemic exposure for T705, compound 4a displayed non inferior anti-influenza activities, compared with its parent drug T705.

Conclusion:

Our prodrugs development strategy for T705 is feasible, which may serves as a reference to prodrugs development of similar heterocyclic amides compounds.
Pharmacokinetics of Picroside I, II, III, IV in Rat Plasma by UPLCMS/ MS
Authors: Xie Haili , Lu Xiaojie , Jin Weiqiang , Zhou Hua , Chen Dongxin , Wang Xianqin , Zhou Yunfang
Published: October 2019

Background:

Modern pharmacological studies show that rhizoma coptidis has protective
effects on the liver, gallbladder, kidney, cerebral ischemia-reperfusion, local hypoxia injury, antiinflammatory,
bone injury, nerve cells and myocardial cells. The effective components have been isolated
from picroside I, II, III and IV.

Introduction:

A selective and sensitive ultra-performance liquid chromatography electrospray ionization
tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed for the simultaneous
quantitative determination of picroside I, II, III and IV in rat plasma to aid the pharmacokinetics studies.

Method:

Sprague-Dawley (SD) rats were orally administered with 10 mg/kg, intravenously injected
with 1 mg/kg for the mixture of picroside I, II, III and IV. The biological samples were collected at
0.083 3 h, 0.25 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h. A UPLC BEH C18 column (2.1 mm×50 mm,
1.7 μm) was used for chromatographic separation with the mobile phase consisting of acetonitrile and
0.1% formic acid by gradient elution. The flow rate was 0.4 mL/min. Multiple reaction monitoring
(MRM) transitions were m/z 491.1→147.1 for picroside I, m/z 511.1→234.9 for picroside II, m/z
537.3→174.8 for picroside III and m/z 507.3→163.1 for picroside IV in negative ion mode.

Result:

The inter-day precision was less than 13%, the intra-day precision was less than 15%. The
accuracy ranged from 89.4% to 111.1%. Recovery was higher than 79.1%, and the matrix effect ranged
from 96.2% to 109.0%.

Conclusion:

The sensitive, rapid and selective UPLC-MS/MS method can be applied to the pharmacokinetic
study of picroside I, II, III and IV in rats.
Mechanism of a Novel Camptothecin-Deoxycholic Acid Derivate Induced Apoptosis against Human Liver Cancer HepG2 Cells and Human Colon Cancer HCT116 Cells
Authors: Xiao Linxia , Xu Jialin , Weng Qi , Zhou Leilei , Wang Mengke , Liu Miao , Li Qingyong
Published: October 2019

Background:

Camptothecin (CPT) is known as an anticancer drug in traditional Chinese medicine. However, due to the lack of targeting, low solubility, and instability of CPT, its therapeutic applications are hampered. Therefore, we synthesized a series of CPT-bile acid analogues that obtained a national patent to improve their tumour-targeting chemotherapeutic effects on liver or colon cancers. Among these analogues, the compound G2 shows high antitumor activity with enhanced liver targeting and improved oral absorption. It is significant to further investigate the possible anticancer mechanism of G2 for its further clinical research and application.

Objective:

We aimed to unearth the anticancer mechanism of G2 in HepG2 and HCT116 cells.

Methods:

Cell viability was measured using MTT assay; cell cycle, Mitochondrial Membrane Potential (MMP), and cell apoptosis were detected by flow cytometer; ROS was measured by Fluorescent Microplate Reader; the mRNA and protein levels of cell cycle-related and apoptosis-associated proteins were examined by RT-PCR and western blot, respectively.

Results:

We found that G2 inhibited cells proliferation of HepG2 and HCT116 remarkably in a dosedependent manner. Moreover, G2-treatment led to S and G2/M phase arrest in both cells, which could be elucidated by the change of mRNA levels of p21, p27 and Cyclin E and the increased protein level of p21. G2 also induced dramatically ROS accumulated and MMP decreased, which contributed to the apoptosis through activation of both the extrinsic and intrinsic pathways via changing the genes and proteins expression involved in apoptosis pathway in both of HepG2 and HCT116 cells.

Conclusion:

These findings suggested that the apoptosis in both cell lines induced by G2 was related to the extrinsic and intrinsic pathways.
MDM2-p53 Interaction Inhibitors: The Current State-of-Art and Updated Patent Review (2010-Present)
Authors: Rusiecki Rafał , Witkowski Jakub , Jaszczewska-Adamczak Joanna
Published: October 2019

Background:

Mouse Double Minute 2 protein (MDM2) is a cellular regulator of p53 tumor suppressor (p53). Inhibition of the interaction between MDM2 and p53 proteins is a promising anticancer therapy.

Objective:

This updated patent review is an attempt to compile the research and achievements of the various researchers working on small molecule MDM2 inhibitors from 2010 to date. We provide an outlook into the future for therapy based on MDM2 inhibition by presenting an overview of the most relevant patents which have recently appeared in the literature.

Methods:

Literature and recent patents focusing on the anticancer potential of MDM2-p53 interaction inhibitors and its applications have been analyzed. We put the main emphasis on the most perspective compounds which are or were examined in clinical trials.

Results:

Literature data indicated that MDM2 inhibitors are therapeutically effective in specific types of cancer or non-cancer diseases. A great number of patents and research work around new MDM2- p53 interaction inhibitors, possible combinations, new indications, clinical regimens in previous years prove that this targeted therapy is in the scope of interest for many business and academic research groups.

Conclusion:

Novel MDM2 inhibitors thanks to higher potency and better ADME properties have shown effectiveness in preclinical and clinical development however the final improvement of therapeutic potential for MDM2 inhibitors might depend on the useful combination therapy and exploring new cancer and non-cancer indications.