Structural characterization of the degradation products of a minor natural sweet diterpene glycoside Rebaudioside M under acidic conditions.

Degradation of rebaudioside M, a minor sweet component of Stevia rebaudiana Bertoni, under conditions that simulated extreme pH and temperature conditions has been studied. Thus, rebaudioside M was treated with 0.1 M phosphoric acid solution (pH 2.0) and 80 °C temperature for 24 h. Experimental results indicated that rebaudioside M under low pH and higher temperature yielded three minor degradation compounds, whose structural characterization was performed on the basis of 1D (1H-, 13C-) & 2D (COSY, HSQC, HMBC) NMR, HRMS, MS/MS spectral data as well as enzymatic and acid hydrolysis studies.

Additional new minor cucurbitane glycosides from Siraitia grosvenorii.

Continuous phytochemical studies of the crude extract of Luo Han Guo (Siraitia grosvenorii) furnished three additional new cucurbitane triterpene glycosides, namely 11-deoxymogroside V, 11-deoxyisomogroside V, and 11-deoxymogroside VI. The structures of all the isolated compounds were characterized on the basis of extensive NMR and mass spectral data as well as hydrolysis studies. The complete ¹H- and ¹³C-NMR spectral assignments of the three unknown compounds are reported for the first time based on COSY, TOCSY, HSQC, and HMBC spectroscopic data.

Structures of some novel α-glucosyl diterpene glycosides from the glycosylation of steviol glycosides.

Four new minor diterpene glycosides with a rare α-glucosyl linkage were isolated from a cyclodextrin glycosyltransferase glucosylated stevia extract containing more than 98% steviol glycosides. The new compounds were identified as 13-[(2-O-ß-D-glucopyranosyl-3-O-(4-O-α-D-glucopyranosyl)-ß-D-glucopyranosyl-ß-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-ß-D-glucopyranosyl) ester] (1), 13-[(2-O-ß-D-glucopyranosyl-ß-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-ß-D-glucopyranosyl ester] (2), 13-[(2-O-ß-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-ß-D-glucopyranosyl-ß-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid ß-D-glucopyranosyl ester (3), and 13-[(2-O-ß-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-ß-D-glucopyranosyl- ß-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-ß-D-glucopyranosyl) ester] (4) on the basis of extensive NMR and mass spectral (MS) data as well as hydrolysis studies.

The role of drought response genes and plant growth promoting bacteria on plant growth promotion under sustainable agriculture: A review.

Drought is a major stressor that poses significant challenges for agricultural practices. It becomes difficult to meet the global demand for food crops and fodder. Plant physiology, physico-chemistry and morphology changes in plants like decreased photosynthesis and transpiration rate, overproduction of reactive oxygen species, repressed shoot and root shoot growth and modified stress signalling pathways by drought, lead to detrimental impacts on plant development and output. Coping with drought stress requires a variety of adaptations and mitigation techniques. Crop yields could be effectively increased by employing plant growth-promoting rhizobacteria (PGPR), which operate through many mechanisms. These vital microbes colonise the rhizosphere of crops and promote drought resistance by producing exopolysaccharides (EPS), 1-aminocyclopropane-1-carboxylate (ACC) deaminase and phytohormones including volatile compounds. The upregulation or downregulation of stress-responsive genes causes changes in root architecture due to acquiring drought resistance. Further, PGPR induces osmolyte and antioxidant accumulation. Another key feature of microbial communities associated with crops includes induced systemic tolerance and the production of free radical-scavenging enzymes. This review is focused on detailing the role of PGPR in assisting plants to adapt to drought stress.

Hydrogenation of the exocyclic olefinic bond at C-16/C-17 position of ent-kaurane diterpene glycosides of Stevia rebaudiana using various catalysts.

Catalytic hydrogenation of the exocyclic double bond present between C16 and C17 carbons of the four ent-kaurane diterpene glycosides namely rebaudioside A, rebaudioside B, rebaudioside C, and rebaudioside D isolated from Stevia rebaudiana has been carried out using Pt/C, Pd(OH)2, Rh/C, Raney Ni, PtO2, and 5% Pd/BaCO3 to their corresponding dihydro derivatives with 17α and 17ß methyl group isomers. Reactions were performed using the above-mentioned catalysts with the solvents methanol, water, and ethanol/water (8:2) under various conditions. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data, including a comparison with reported spectral data.

Additional minor diterpene glycosides from Stevia rebaudiana Bertoni.

Two additional novel minor diterpene glycosides were isolated from the commercial extract of the leaves of Stevia rebaudiana Bertoni. The structures of the new compounds were identified as 13-{ß-D-glucopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)-ß-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucupyranosyl-ester} (1), and 13-{ß-D-6-deoxy-glucopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)-ß-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {ß-D-glucopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)-ß-D-gluco-pyranosyl-ester} (2), on the basis of extensive 1D (1H- and 13C-) 2D NMR (COSY, HSQC and HMBC) and MS spectroscopic data as well as chemical studies.

Interdisciplinary treatment of an adolescent with unilateral cleft lip and palate.

AIM: The present case report describes the importance of interdisciplinary approach and gives an understanding on management of an adolescent with unilateral cleft lip and palate. BACKGROUND: Failure of fusion between medial nasal process and maxillary process or between the palatal process leads to the formation of clefts. Clefts are result of genetic or environmental factors or a combination of both. Common dental problems associated with clefts includes anterior and posterior crossbites, hypodontia, malformation and abnormal eruption pattern. CASE REPORT: A girl, aged 15 years reported with a chief complaint of unesthetic appearance of her maxillary anterior teeth. She had unilateral cleft lip and palate and had received cheiloplasty and palatoplasty when she was in young age and rhinoplasty when she was 14 years of age. At pretreatment evaluation, she had concave profile with maxillary arch constriction and oroantral fistula and mesially tipped maxillary left canine. CONCLUSION: This patient's treatment was unconventional, but it was successful in significantly improving her masticatory function and smile, along with favorable dental and facial results. Generalized esthetics and function were significantly improved in this patient without orthognathic surgery, and treatment results were stable 3 years after the appliance removal. Clinical considerations, sequencing of treatment phases as shown in this case report can be utilized while treating an adolescent with cleft lip and palate. CLINICAL SIGNIFICANCE: If the skeletal discrepancy is mild and esthetic concerns are minimal, dental compensation by orthodontic treatment alone might be recommended. The cephalometric analysis and prediction tracings provide further information for deciding whether a patient can be treated by orthodontics alone, or by orthodontics and an orthognathic surgical procedure. A change in axial inclination of the teeth can camouflage the skeletal relationship adequately. However, one should be cautious in a growing patient, because he or she might outgrow the dental correction so that ultimately skeletal surgery would be indicated.

Catalytic hydrogenation of the sweet principles of Stevia rebaudiana, Rebaudioside B, Rebaudioside C, and Rebaudioside D and sensory evaluation of their reduced derivatives.

Catalytic hydrogenation of rebaudioside B, rebaudioside C, and rebaudioside D; the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana was carried out using Pd(OH)(2). Reduction of steviol glycosides was performed using straightforward synthetic chemistry with the catalyst Pd(OH)(2) and structures of the corresponding dihydro derivatives were characterized on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectral data indicating that all are novel compounds being reported for the first time. Also, the taste properties of all reduced compounds were evaluated against their corresponding original steviol glycosides and sucrose.

Synthesis and sensory evaluation of ent-kaurane diterpene glycosides.

Catalytic hydrogenation of the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana, namely rubusoside, stevioside, and rebaudioside-A has been carried out using Pd(OH)2 and their corresponding dihydro derivatives have been isolated as the products. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data and chemical studies. Also, we report herewith the sensory evaluation of all the reduced compounds against their corresponding original steviol glycosides and sucrose for the sweetness property of these molecules.

Biomechanical and clinical considerations in correcting skeletal class II malocclusion with Forsus™.

AIM: The present case report describes the importance of understanding of biomechanical and clinical considerations in application of Forsus appliance in correction of class II skeletal malocclusion. BACKGROUND: Angle's class II malocclusion is one of the most prevailing that may be either skeletal or dental presenting with different clinical manifestations. There are number of appliances to treat such a malocclusion in a growing child. Fixed functional appliances are indicated for class II corrections in patients who report late with minimal residual growth left. CASE DESCRIPTION: A case of class II skeletal and dental malocclusion treated with preadjusted edgewise appliance supplemented with Forsus Fatigue Resistant Device (FRD) (3M Unitek Corp, California, USA) is reported. CONCLUSION: Forsus device is an effective alternative in treating moderate skeletal class II malocclusion. The Forsus FRD (3M Unitek Corp, California, USA) can be used instead of class II elastics in mild cases and in place of Herbst appliance in severe cases. Alteration of force vector by modifying the archwire as shown in this case report while applying Forsus and incorporation of 10 degree labial root torque in lower archwire will minimize the effects on dentition. Engaging modules or tubing on to the pushrod and leaving 1 to 2 mm clearance between distal end of the upper tube and L-pin as shown in this case report will significantly improve the patient compliance. CLINICAL SIGNIFICANCE: Much emphasis should be given to biomechanical considerations which were discussed in this article while treating patients with Forsus to prevent the unwanted effects. Clinical considerations and certain modifications advised in this case report should be utilized while treating class II skeletal malocclusions with Forsus appliance to eliminate the patient cooperation factor and make treatment time estimates much more accurate.

A Systematic Review of the Link Between Autism Spectrum Disorder and Acetaminophen: A Mystery to Resolve.

The purpose of this study is to review the published papers investigating maternal acetaminophen (AP) use during pregnancy and its effect on the offspring's neurodevelopment, particularly autism spectrum disorders (ASD). Acetaminophen is an over-the-counter analgesic and antipyretic considered safe in pregnancy. Recent studies have found an association between acetaminophen and immune system alterations like asthma and adverse neurodevelopmental outcomes. We used online databases (PubMed/Medline/PubMed Central, Science Direct, and Google Scholar) to search the studies relevant to our topic. We screened the papers by titles, abstracts, and then full-text availability. The screened articles were checked for eligibility using relevant quality assessment tools for each study design, extracting and analyzing the data. We finalized 30 studies after the screening; 14 were ineligible. Our final selection included 16 high-quality papers - 13 prospective cohort studies, two review articles, and one meta-analysis. We found a wide range of neurodevelopmental outcomes in our data collection. So, we included autism spectrum disorders, intelligent quotient (IQ), attention-deficit/hyperactivity disorder (ADHD), isolated language, attention and executive function, communication, behavior, and psychomotor development. All studies showed an association between acetaminophen use and listed neurodevelopmental outcomes. Long-term use, increased dose, and frequency were associated with a stronger association. We extracted collective evidence from 16 studies suggesting acetaminophen's role in developing adverse neurodevelopmental outcomes. It is urgent to do more research on this association before pregnant women can be cautioned about the precise use of acetaminophen.

Diterpene glycosides from Stevia rebaudiana.

Three novel diterpene glycosides were isolated for the first time from the commercial extract of the leaves of Stevia rebaudiana, along with several known steviol glycosides, namely stevioside, rebaudiosides A-F, rubusoside and dulcoside A. The new compounds were identified as 13-[(2-O-ß-D-glucopyranosyl-3-O-ß-D-glucopyranosyl-ß-D-glucopyranosyl)oxy] ent-kaur-15-en-19-oic acid, 13-[(2-O-ß-D-glucopyranosyl-3-O-ß-D-glucopyranosyl-ß-D-glucopyranosyl)oxy]-16ß-hydroxy-ent-kauran-19-oic acid and 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-ß-D-glucopyranosyl ester on the basis of extensive 2D NMR and MS spectroscopic data as well as chemical studies.

A new diterpene glycoside from Stevia rebaudiana.

From the commercial extract of the leaves of Stevia rebaudiana, a new diterpene glycoside was isolated besides the known steviol glycosides including stevioside, rebaudiosides A-F, rubusoside and dulcoside A. The new compound was identified as 13-[(2-O-ß-D-glucopyranosyl-3-O-ß-D-glucopyranosyl-ß-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-(2-O-α-L-rhamnopyranosyl-ß-D-glucopyranosyl) ester (1) on the basis of extensive spectroscopic (NMR and MS) and chemical studies.

Synthesis of ent-kaurane diterpene monoglycosides.

Synthesis of two ent-kaurane diterpene glycosides, steviol 19-O-ß-D-glucopyranosiduronic acid (steviol glucuronide, 5), and 13-hydroxy ent-kaur-16-en-19-oic acid-ß-D-glucopyranosyl ester (7) has been achieved from a common starting material, steviol, using phase transfer catalyst. Also, synthesis of an additional 17-nor-ent-kaurane glycoside, namely 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-ß-D-glucopyranosyl ester (10) was performed using the starting material isosteviol and similar synthetic methodology. Synthesis of all three steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR as well as mass spectral (MS) data.

Chain length of bioinspired polyamines affects size and condensation of monodisperse silica particles.

Polyamines play a major role in biosilicification reactions in diatoms and sponges. While the effects of polyamines on silicic acid oligomerization and precipitation are well known, the impact of polyamines chain length on silica particle growth is unclear. We studied the effects of polyamine chain length on silica particle growth and condensation in a known, simple, and salt-free biphasic reaction system; with tetraethyl orthosilicate as organic phase and polyamine dissolved in the aqueous phase. The particles at various growth stages were characterized by Cryo- Transmission Electron Microscopy, Scanning Electron Microscopy, Thermogravimetric Analysis, Zeta Potential, and solid-state NMR analysis. Polyamines were found co-localized within silica particles and the particle diameter increased with an increase in polyamine chain length, whereas silica condensation showed the opposite trend. Particle growth is proposed to progress via a coacervate intermediate while the final particles have a core shell structure with an amine-rich core and silica-rich shell. The results presented in this paper would of interest for researchers working in the field of bioinspired materials.

Modifying the thickness, pore size, and composition of diatom frustule in Pinnularia sp. with Al3+ ions.

Diatoms are unicellular photosynthetic algae that produce a silica exoskeleton (frustule) which exposes a highly ordered nano to micro scale morphology. In recent years there has been a growing interest in modifying diatom frustules for technological applications. This is achieved by adding non-essential metals to the growth medium of diatoms which in turn modifies morphology, composition, and resulting properties of the frustule. Here, we investigate the frustule formation in diatom Pinnularia sp., including changes to overall morphology, silica thickness, and composition, in the presence of Al3+ ions at different concentrations. Our results show that in the presence of Al3+ the total silica uptake from the growth medium increases, although a decrease in the growth rate is observed. This leads to a higher inorganic content per diatom resulting in a decreased pore diameter and a thicker frustule as evidenced by electron microscopy. Furthermore, 27Al solid-state NMR, FIB-SEM, and EDS results confirm that Al3+ becomes incorporated into the frustule during the silicification process, thus, improving hydrolysis resistance. This approach may be extended to a broad range of elements and diatom species towards the scalable production of silica materials with tunable hierarchical morphology and chemical composition.

Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers.

CPT-11, also known as irinotecan, is a prodrug that is approved for the treatment of advanced colorectal cancer. The active metabolite of CPT-11, SN38 (7-ethyl-10-hydroxy-camptothecin), has 100- to 1000-fold more potent cytotoxic activity in tissue cell culture compared with CPT-11. However, parental administration of SN38 is not possible because of its inherently poor water solubility. It is reported here that a multiarm poly(ethylene glycol) (PEG) backbone linked to four SN38 molecules (PEG-SN38) has been successfully prepared with high drug loading and significantly improved water solubility (400- to 1000-fold increase). Three different protecting strategies have been developed in order to selectively acylate the 20-OH of SN38 to preserve its E-ring in the lactone form (the active form of SN38 with cytotoxic activities) while PEG is still attached. One chemical process has been optimized to make a large quantity of the PEG-SN38 conjugate with a high yield that can be readily adapted for scale-up production. The PEG-SN38 conjugates have shown excellent in vitro anticancer activity, with potency similar to that of native SN38, in a panel of cancer cell lines. The PEG-SN38 conjugates also have demonstrated superior anticancer activity in the MX-1 xenograft mice model compared with CPT-11. Among the four conjugates, PEG-Gly-(20)-SN38 (23) has been selected as the lead candidate for further preclinical development.

Flexibility of components alters the self-assembly pathway of Pd2L4 coordination cages.

The self-assembly process of a Pd2L4 cage consisting of flexible ditopic ligands and Pd(ii) ions was revealed by QASAP (quantitative analysis of self-assembly process), which enables one to obtain information about the intermediates transiently produced during the self-assembly as the average composition of all the intermediates. It was found that the dominant pathway to the cage is the formation of a submicrometre-sized sheet structure, which was characterized by dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM), followed by the addition of free ditopic ligands to the Pd(ii) centres of the sheet structure to trigger the cage formation. This assembly process is completely different from that of a Pd2L4 cage composed of rigid ditopic ligands, indicating that the flexibility of the components strongly affects the self-assembly process.

Heterogeneous catalase-like activity of gold(i)-cobalt(iii) metallosupramolecular ionic crystals.

Unique heterogeneous catalase-like activity was observed for metallosupramolecular ionic crystals [AuI4CoIII2(dppe)2(d-pen)4]X n ([1]X n ; dppe = 1,2-bis(diphenylphosphino)ethane; d-pen = d-penicillaminate; X n = (Cl-)2, (ClO4-)2, (NO3-)2 or SO42-) consisting of AuI4CoIII2 complex cations, [1]2+, and inorganic anions, X- or X2-. Treatment of the ionic crystals with an aqueous H2O2 solution led to considerable O2 evolution with a high turnover frequency of 1.4 × 105 h-1 for the heterogeneous cobalt complexes, which was dependent on their size and shape as well as the arrangement of cationic and anionic species. These dependencies were rationalized by the presence of cobalt(ii) centers on the crystal surface and their efficient exposure on the (111) plane rather than the (100) plane based on morphological and theoretical studies.