Prediction of osteoporotic fractures by postural instability and bone density.

OBJECTIVE--To investigate the utility of risk factors such as bone mineral density, lifestyle, and postural stability in the prediction of osteoporotic fractures. DESIGN--Longitudinal, epidemiological, and population based survey. SETTING--City of Dubbo, New South Wales. SUBJECTS--All residents of Dubbo aged > or = 60 on 1 January 1989. MAIN OUTCOME MEASURE--Incidence of fracture for individual subjects. RESULTS--The overall incidence of atraumatic fractures in men and women was 1.9% and 3.1% per annum respectively. The predominant sites of fracture were hip (18.9%), distal radius (18.5%), ribs and humerus (11.9% in each case), and ankle and foot (9.1% and 6.6% respectively). Major predictors of fractures in men and women were femoral neck bone mineral density, body sway, and quadriceps strength. Age, years since menopause, height, weight, and lifestyle factors were also correlated with bone mineral density and body sway and hence were indirect risk factors for fracture. Discriminant function analysis correctly identified 96% and 93% (sensitivities 88% and 81%) of men and women, respectively, who subsequently developed atraumatic fractures. Predictions based on this model indicated that a woman with a bone mineral density in the lowest quartile in the hip together with high body sway had a 8.4% probability of fracture per annum. This represented an almost 14-fold increase in risk of fracture compared with a woman in the highest bone mineral density quartile with low postural sway. An individual with all three predictors in the "highest risk" quartile had a 13.1% risk of fracture per annum. CONCLUSIONS--Bone mineral density, body sway, and muscle strength are independent and powerful synergistic predictors of fracture incidence.     

“DNA signaturing” database construction for Tetradesmus species identification and phylogenetic relationships of Scenedesmus-like green microalgae (Scenedesmaceae,Chlorophyta)

Species identification of Scenedesmus-like microalgae, comprising Desmodesmus, Tetradesmus, and Scenedesmus, has been challenging due to their high morphological and genetic similarity. After developing a DNA signaturing tool for Desmodesmus identification, we built a DNA signaturing database for Tetradesmus. The DNA signaturing tool contained species-specific nucleotide sequences of Tetradesmus species or strain groups with high similarity in ITS2 sequences. To construct DNA signaturing, we collected data on ITS2 sequences, aligned the sequences, organized the data by ITS2 sequence homology, and determined signature sequences according to hemi-compensatory base changes (hCBC)/CBC data from previous studies. Four Tetradesmus species and 11 strain groups had DNA signatures. The signature sequence of the genus Tetradesmus, TTA GAG GCT TAA GCA AGG ACCC, recognized 86% (157/183) of the collected Tetradesmus strains. Phylogenetic analysis of Scenedesmus-like species revealed that the Tetradesmus species were monophyletic and closely related to each other based on branch lengths. Desmodesmus was suggested to split into two subgenera due to their genetic and morphological distinction. Scenedesmus must be analyzed along with other genera of the Scenedesmaceae family to determine their genetic relationships. Importantly, DNA signaturing was integrated into a database for identifying Scenedesmus-like species through BLAST.     

Environmental conditions during glycerol bioconversion affect 3-hydroxypropionic acid bioproduction by Limosilactobacillus reuteri DSM 17938

3-Hydroxypropionic acid (3-HP) is a platform molecule whose biological production was carried out by the bacterium Limosilactobacillus reuteri according to a two-step process: first, a growth phase in batch mode on glucose, then a glycerol bioconversion into 3-HP in fed-batch mode. With the objective of improving 3-HP bioproduction, this study aimed at defining the operating conditions during the bioconversion phase that increases the bioproduction performance. A central composite rotatable design allowed testing various pH levels and specific glycerol feeding rates. By establishing response surfaces, optimal conditions have been identified that were different depending on the considered output variable (final 3-HP quantity, 3-HP production yield and production rate). Of them, 3-HP final quantity and 3-HP production yield were maximized at pH 6.0 and at specific glycerol feeding rates of 60 and 55 mg_gly g_CDW⁻¹ h⁻¹, respectively. The specific 3-HP production rate was the highest at the upper limit of the specific substrate feeding rate (80 mg_gly g_CDW⁻¹ h⁻¹) but was not affected by the pH. An additional experiment was carried out at pH 6.0 and a specific glycerol feeding rate of 80 mg_gly g_CDW⁻¹ h⁻¹ to validate the previous observations. In conclusion, the results showed a significant improvement of 3-HP concentration by 13%, of specific production rate by 34% and of 3-HP volumetric productivity by 39%, as compared to the initial values.     

New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production

A new isopropyl chromone ( 1 ) and a new flavanone glucoside ( 2 ) together with eleven known compounds ( 3–13 ) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one ( 1 ), 5,7-dihydroxyflavanone 7-O-β-D-(6′′-O-galloylglucopyranoside) ( 2 ), strobopinin ( 3 ), demethoxymatteucinol ( 4 ), pinocembrin-7-O-β-D-glucopyranoside ( 5 ), (2S)-hydroxynaringenin-7-O-β-D-glucopyranoside ( 6 ), afzelin ( 7 ), quercetin ( 8 ), kaplanin ( 9 ), endoperoxide G3 ( 10 ), grasshopper ( 11 ), vomifoliol ( 12 ), litseagermacrane ( 13 ) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1 , 2 , 5 , 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC₅₀ values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 μM, respectively, while the IC₅₀ values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 μM, compared to that of the positive control, N^G-monomethyl-L-arginine acetate (L-NMMA) with an IC₅₀ value of 32.50±1.00 μM.     

Chemical Profile and Biological Activities of Fungal Strains Isolated from Piper nigrum Roots: Experimental and Computational Approaches

The current report describes the chemical investigation and biological activity of extracts produced by three fungal strains Fusarium oxysporum, Penicillium simplicissimum, and Fusarium proliferatum isolated from the roots of Piper nigrum L. growing in Vietnam. These fungi were namely determined by morphological and DNA analyses. GC/MS identification revealed that the EtOAc extracts of these fungi were associated with the presence of saturated and unsaturated fatty acids. These EtOAc extracts showed cytotoxicity towards cancer cell lines HepG2, inhibited various microbacterial organisms, especially fungus Aspergillus niger and yeast Candida albicans (the MIC values of 50–100 μg/mL). In α-glucosidase inhibitory assay, they induced the IC₅₀ values of 1.00-2.53 μg/mL were better than positive control acarbose (169.80 μg/mL). The EtOAc extract of F. oxysporum also showed strong anti-inflammatory activity against NO production and PGE-2 level. Four major compounds linoleic acid (37.346 %), oleic acid (27.520 %), palmitic acid (25.547 %), and stearic acid (7.030 %) from the EtOAc extract of F. oxysporum were selective in molecular docking study, by which linoleic and oleic acids showed higher binding affinity towards α-glucosidase than palmitic and stearic acids. In subsequent docking assay with inducible nitric oxide synthase (iNOS), palmitic acid, oleic acid and linoleic acid could be moderate inhibitors.     

Environmentally-Friendly Pesticidal Activities of Callicarpa and Karomia Essential Oils from Vietnam and Their Microemulsions

There is an ongoing interest to identify alternative pesticidal agents to avoid the chronic problems associated with synthetic pesticides. Essential oils have shown promise as botanical pest control agents. In the present study, the essential oils of four members of the Lamiaceae (Callicarpa candicans, C. erioclona, C. macrophylla, and Karomia fragrans; Vietnamese names: Nàng nàng, Tu châu lông mem, Tu châu lá to and Cà diện, respectively), obtained from wild populations in Vietnam, have been obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. The essential oils were formulated into microemulsions and the essential oils and their microemulsions were screened for mosquito larvicidal activity against Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and for molluscicidal activity against Pomacea canaliculata. Atractylone and (E)-caryophyllene dominated the volatiles of C. candicans (CCEO) and C. erioclona (CEEO), while the major component in C. macrophylla (CMEO) and K. fragrans (KFEO) was (E)-caryophyllene. The essential oils and microemulsions of both C. candicans and C. erioclona exhibited excellent larvicidal activity against all three mosquito species (Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus) with LC₅₀ values <10 μg/mL. Additionally, the larvicidal activity of the microemulsions were significantly improved compared with their free essential oils, especially for C. candicans and C. erioclona. All four essential oils and their microemulsions showed excellent molluscicidal activity with LC₅₀ <10 μg/mL. In most cases, the essential oils and microemulsions showed greater pesticidal activity against target organisms than the non-target freshwater fish, Oreochromis niloticus. The in silico studies on physicochemical and ADMET properties of the major components in the studied essential oils were also investigated and most of the compounds possessed a favorable ADMET profile. Computational modeling studies of the studied compounds demonstrated a favorable binding interaction with the mosquito odorant-binding protein target and support atractylone, β-selinene, and caryophyllene oxide as potential inhibitors. Based on the observed pesticidal activities of the essential oils and their microemulsions, the Callicarpa species and K. fragrans should be considered for potential cultivation and further exploration as botanical pesticidal agents.     

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design,Synthesis and Bioevaluation

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC₅₀ of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC₅₀ values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.     

A transformer architecture for retention time prediction in liquid chromatography mass spectrometry-based proteomics

Accurate retention time (RT) prediction is important for spectral library-based analysis in data-independent acquisition mass spectrometry-based proteomics. The deep learning approach has demonstrated superior performance over traditional machine learning methods for this purpose. The transformer architecture is a recent development in deep learning that delivers state-of-the-art performance in many fields such as natural language processing, computer vision, and biology. We assess the performance of the transformer architecture for RT prediction using datasets from five deep learning models Prosit, DeepDIA, AutoRT, DeepPhospho, and AlphaPeptDeep. The experimental results on holdout datasets and independent datasets exhibit state-of-the-art performance of the transformer architecture. The software and evaluation datasets are publicly available for future development in the field.     

Crystal structure and conformational analysis of ampullosporin A.

Ampullosporin A is a 15-mer peptaibol type polypeptide that induces pigment formation by the fungus Phoma destructiva, forms voltage-dependent ion channels in membranes and exhibits hypothermic effects in mice. The structure of ampullosporin A has been determined by x-ray crystallography. This is the first three-dimensional (3D) structure of the peptaibol subfamily SF6. From the N-terminus to residue 13 the molecule adopts an approximate right-handed alpha-helical geometry, whereas a less regular structure pattern with beta-turn characteristics is found in the C-terminus. Even though ampullosporin A does not contain a single proline or hydroxyproline it is significantly bent. It belongs to both the shortest and the most strongly bent peptaibol 3D structures. The straight structure part encompasses residues Ac-Trp(1)-Aib(10) and is thus less extended than the alpha-helical subunit. The 3D structure of ampullosporin A is discussed in relation to other experimentally determined peptaibol structures and in the context of its channel-forming properties. As a part of this comparison a novel bending analysis based on a 3D curvilinear axis describing the global structural characteristics has been proposed and applied to all 3D peptaibol structures. A sampling of 2500 conformations using different molecular dynamics protocols yields, for the complete ampullosporin A structure, an alpha-helix as the preferred conformation in vacuo with almost no bend. This indicates that solvent or crystal effects may be important for the experimentally observed peptide backbone bending characteristics of ampullosporin A.