The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches.

Classically, white adipose tissue (WAT) was considered an inert component of connective tissue but is now appreciated as a major regulator of metabolic physiology and endocrine homeostasis. Recent work defining how WAT develops and expands in vivo emphasizes the importance of specific locations of WAT or depots in metabolic regulation. Interestingly, mature white adipocytes are integrated into several tissues. A new perspective regarding the in vivo regulation and function of WAT in these tissues has highlighted an essential role of adipocytes in tissue homeostasis and regeneration. Finally, there has been significant progress in understanding how mature adipocytes regulate the pathology of several diseases. In this review, we discuss these novel roles of WAT in the homeostasis and regeneration of epithelial, muscle, and immune tissues and how they contribute to the pathology of several disorders.

Emergence of methicillin resistance predates the clinical use of antibiotics.

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two ß-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

Anthelmintic efficacy of an organic fraction from Guazuma ulmifolia leaves and evaluation of reactive oxidative stress on Haemonchus contortus.

This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from Guazuma ulmifolia leaves and the evaluation of its reactive oxidative stress on Haemonchus contortus. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (Meriones unguiculatus) artificially infected with H. contortus infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against H. contortus L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p<0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in H. contortus L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (1), leucoanthocyanidin derivative (2), coniferyl alcohol (3), ferulic acid methyl ester acetate (4), 2,3,4-trimethoxycinnamic acid (5) and epiyangambin (6) as major compounds. According to these results, the EtOAc-F from G. ulmifolia leaves exhibit anthelmintic effect and increased the stress biomarkers on H. contortus.

Effects of GLP-1 receptor agonists on neurological complications of diabetes.

Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.

High-Resolution Liquid Chromatography-Mass Spectrometry-Based Metabolomics for the Classification of Chuquiraga (Barnadesioideae, Asteraceae): New Phenylpropanoid Derivatives as Chemical Markers for Chuquiraga spinosa.

Despite their relatively poorly investigated phytochemistry, species of the genus Chuquiraga are widely commercialized. The present study reports the use of a high-resolution liquid chromatography-mass spectrometry-based metabolomics approach coupled with exploratory and supervised multivariate statistical analyses for species classification and chemical marker identification of four species of Chuquiraga (C. jussieui, C. weberbaueri, C. spinosa, and Chuquiraga sp.) from Ecuador and Peru. Based on these analyses, a high percentage of correct classifications (87% to 100%) allowed the prediction of the taxonomic identity of Chuquiraga species. Through the metabolite selection process, several key constituents with the potential to be chemical markers were identified. Samples of C. jussieui displayed alkyl glycosides and triterpenoid glycosides as discriminating metabolites, while Chuquiraga sp. displayed high concentrations of p-hydroxyacetophenone, p-hydroxyacetophenone 4-O-glucoside, p-hydroxyacetophenone 4-O-(6-O-apiosyl)-glucoside, and quinic acid ester derivatives as the main metabolites. Caffeic acid was characteristic for C. weberbaueri samples, whereas C. spinosa displayed higher concentrations of the following new phenylpropanoid ester derivatives: 2-O-caffeoyl-4-hydroxypentanedioic acid (24), 2-O-p-coumaroyl-4-hydroxypentanedioic acid (34), 2-O-feruloyl-4-hydroxypentanedioic acid (46), 2,4-O-dicaffeoylpentanedioic acid (71), and 2-O-caffeoyl-4-O-feruloylpentanedioic acid (77).

Negation recognition in clinical natural language processing using a combination of the NegEx algorithm and a convolutional neural network.

BACKGROUND: Important clinical information of patients is present in unstructured free-text fields of Electronic Health Records (EHRs). While this information can be extracted using clinical Natural Language Processing (cNLP), the recognition of negation modifiers represents an important challenge. A wide range of cNLP applications have been developed to detect the negation of medical entities in clinical free-text, however, effective solutions for languages other than English are scarce. This study aimed at developing a solution for negation recognition in Spanish EHRs based on a combination of a customized rule-based NegEx layer and a convolutional neural network (CNN). METHODS: Based on our previous experience in real world evidence (RWE) studies using information embedded in EHRs, negation recognition was simplified into a binary problem ('affirmative' vs. 'non-affirmative' class). For the NegEx layer, negation rules were obtained from a publicly available Spanish corpus and enriched with custom ones, whereby the CNN binary classifier was trained on EHRs annotated for clinical named entities (cNEs) and negation markers by medical doctors. RESULTS: The proposed negation recognition pipeline obtained precision, recall, and F1-score of 0.93, 0.94, and 0.94 for the 'affirmative' class, and 0.86, 0.84, and 0.85 for the 'non-affirmative' class, respectively. To validate the generalization capabilities of our methodology, we applied the negation recognition pipeline on EHRs (6,710 cNEs) from a different data source distribution than the training corpus and obtained consistent performance metrics for the 'affirmative' and 'non-affirmative' class (0.95, 0.97, and 0.96; and 0.90, 0.83, and 0.86 for precision, recall, and F1-score, respectively). Lastly, we evaluated the pipeline against two publicly available Spanish negation corpora, the IULA and NUBes, obtaining state-of-the-art metrics (1.00, 0.99, and 0.99; and 1.00, 0.93, and 0.96 for precision, recall, and F1-score, respectively). CONCLUSION: Negation recognition is a source of low precision in the retrieval of cNEs from EHRs' free-text. Combining a customized rule-based NegEx layer with a CNN binary classifier outperformed many other current approaches. RWE studies highly benefit from the correct recognition of negation as it reduces false positive detections of cNE which otherwise would undoubtedly reduce the credibility of cNLP systems.

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats.

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFß, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.

SOD2 Gene Variants (rs4880 and rs5746136) and Their Association with Breast Cancer Risk.

The superoxide dismutase (SOD) is the principal antioxidant defense system in the body that is activated by a reactive oxygen species. Some variants of the SOD2 gene have been associated with cancer. The rs4880 variant was determined by PCR real-time and the rs5746136 variant by PCR-RFLP in healthy subjects and in breast cancer (BC) patients. The rs4880 and rs5746136 variants were associated with BC susceptibility when BC patients and the control group were compared for the CT, TT, CTCC, and the T alleles (p < 0.05). The CT genotype of the rs4880 variant showed significant statistical differences in patients and controls aged ≤ 45 years old, and with hormonal consumption (p < 0.05). The rs4880 variant was associated with BC patients with CTTT genotype and obesity, the presence of DM2-SAH, and a non-chemotherapy response (p < 0.05). Additionally, the rs5746136 variant was associated with susceptibility to BC with Ki-67 (≥20%), luminal A type BC, and a chemotherapy partial response (p < 0.05) in BC patients who carry TT, TC, and CTTT genotypes, respectively. The haplotype T/T (OR 1.98; 95% CI 1.20−3.26, p = 0.005) was observed to be a risk factor for BC. The rs4880 and rs5746136 variants in the SOD2 gene were associated with BC susceptibility.

Constituents of Croton megalocarpus with Potential Anti-HIV Activity.

Reported herein is an anti-HIV monochlorinated compound, 1ß-acetoxy-3ß-chloro-5α,6α-dihydroxycrotocascarin L (1), of the rare crotofolane diterpenoid class. Compound 1, a suspected artifact of extraction, along with the previously undescribed 11ß-acetoxycrotocascarin L (2) and a known compound, crotocascarin K (3), were isolated from the bark of Croton megalocarpus, a Kenyan oil-producing seed crop. Compounds 1 and 3 inhibited HIV-1 replication with IC50 values of 28 and 5.5 nM, respectively. Furthermore, both compounds lacked cytotoxicity toward MT-4 cells and FM-55-M1 cells at concentrations of up to 50 µM. Compounds 1 and 3 were both found to inhibit HIV-1 protease.

First Report of Fusarium verticillioides Causing Cucumber Fruit Rot in Sinaloa, Mexico.

Cucumber (Cucumis sativus L.) is a fruit crop with high consumption worldwide. Mexico had a cucumber production of 826,485 tonnes in 2019. In December 2020, in a greenhouse in Sinaloa State, 18% of persian cucumber fruits with rot symptoms and the development of cottony white mycelia at both ends were observed similar to those described for Fusarium incarnatum (Garcia-Estrada et al., 2021). Isolation of the causal agent was carried out on PDA medium at 27°C for seven days from disinfested sections of cucumber tissues in NaOCl at 1% for one minute and then rinsed in distilled water. Morphological characterization was carried out on SNA medium, in which cultures was colorless and showed scarcely mycelia growth; however, microconidia were abundant and mainly showed clavate shaped measuring 16.6±2.2 x 5.32±1.0 µm (n=100). The morphological characteristics were similar to those described for Fusarium verticillioides (Nirenberhg, 1981). To confirm the species identity, the internal transcribed spacer (ITS) region and the actin (ACT), ß-tubulin (B-tub), calmodulin (CAL), and translation elongation factor 1-α (TEF1-α) genes were amplified and sequenced from one representative isolate: FPM03. These sequences were submitted to GenBank with the accession number MZ868200 for the ITS region and MZ955274 to MZ955277 for the ACT, B-tub, CAL, and TEF1-α regions. BLASTn analysis of the sequences showed 99 to 100% identity with several F. verticillioides sequence accession numbers MG515226, KU603765, MW402311, MW402449, and MW402113, which corresponded to strains CM1, CBS 576.78, and CBS 218.76. To evaluate Koch's postulates, ten healthy cucumber fruits were disinfected with 1% NaOCl for one min and then washed with distilled water. The fruits were inoculated with a single-spore suspension (3 × 104 conidia/mL) by spraying, as well as, five two-month-old cucumber plants. For controls, ten cucumber fruits and five plants were sprayed with sterile distilled water. All fruits were incubated in plastic bags at 25°C for four days and plants were placed under greenhouses conditions for a week. At 30 h after inoculation, all inoculated fruits showed soft rot symptoms at the fruit poles, and the development of white and cottony mycelia was observed at 48 h. Inoculated plants showed the symptoms mainly in the flower end of the fruits after three days. The symptoms observed under laboratory conditions were similar to those registered initially in the field. Samples of rotted tissues (fruit ends and flowers) from inoculated fruits were cultured on PDA medium; the resultant colonies showed similar characteristics to those obtained initially and the same pathogen was recovered. All control fruits and plants remained healthy, confirming pathogenicity. Fusarium verticillioides is primarily a maize pathogen causing stalk and ear rots globally, resulting in significant yield losses and reductions in grain quality; besides, this species produces large amounts of fumonisin B1 with high toxigenicity and is frequently found as food contaminant (Leslie and Sumerell, 2006). In addition, this pathogen was reported to affect sweet sorghum in Spain and banana in Jordan (Palmero et al., 2012; Salem et al., 2020). Recently, in Mexico, F. incarnatum was reported to cause soft rot in cucumber fruits (Garcia-Estrada et al., 2021); however, this is the first report of F. verticillioides affecting Mexican cucumber production. This information will be relevant for disease prevention and control.

Two-Dimensional Titanium Dioxide-Surfactant Photoactive Supramolecular Networks: Synthesis, Properties, and Applications for the Conversion of Light Energy.

The desire to harness solar energy to address current global environmental problems led us to investigate two-dimensional (2D) core-shell hybrid photocatalysts in the form of a 2D-TiO2-surfactant, mainly composed of fatty acids. The bulk products, prepared by two slightly different methods, consist of stacked host-guest hybrid sheets held together by van der Waals forces between alkyl carboxylate moieties, favoring the synergistic conjugation of the photophysical properties of the core and the hydrophobicity of the self-assembled surfactant monolayer of the shell. X-ray diffraction and the vibrational characteristics of the products revealed the influence of synthesis strategies on two types of supramolecular aggregates that differ in the core chemical structure, guest conformers of alkyl surfactant tails and type, and the bilayer and monolayer of the structure of nanocomposites. The singular ability of the TiO2 core to anchor carboxylate leads to commensurate hybrids, in contrast to both layered clay and layered double-hydroxide-based ion exchangers which have been previously reported, making them potentially interesting for modeling the role of fatty acids and lipids in bio-systems. The optical properties and photocatalytic activity of the products, mainly in composites with smaller bandgap semiconductors, are qualitatively similar to those of nanostructured TiO2 but improve their photoresponse due to bandgap shifts and the extreme aspect-ratio characteristics of two-dimensional TiO2 confinement. These results could be seen as a proof-of-concept of the potential of these materials to create custom-designed 2D-TiO2-surfactant supramolecular photocatalysts.

Suicide Risk in Rheumatoid Arthritis Patients is Associated With Suboptimal Vitamin D Levels.

BACKGROUND/OBJECTIVE: Rheumatoid arthritis (RA) patients might experience anxiety and depressive symptoms. Deficient vitamin D levels may be a trigger for these conditions. The aim of this study was to determine the frequency of depression, anxiety symptoms, and suicidal risk or ideation in patients with RA associated with vitamin D serum levels. METHODS: In this cross-sectional study, we recruited RA patients older than 18 years, classified into 3 groups according to serum vitamin D levels: sufficient, ≥30 ng/mL; insufficient, 20-29 ng/mL; and deficient, <20 ng/mL. Based on the self-reported Plutchik and the Hospital Anxiety and Depression Scale, we evaluated the association of suicidal risk, depression, and anxiety with the vitamin D levels in RA and the Rheumatoid Arthritis Quality-of-Life Questionnaire. RESULTS: We studied 72 patients with RA between January and October 2019. We found an inverse correlation between Plutchik score and suicidal risk with inadequate vitamin D levels, but not with the Hospital Anxiety and Depression Scale. Suicidal ideation was associated with a higher score on the Rheumatoid Arthritis Quality-of-Life Questionnaire. CONCLUSIONS: Despite the high prevalence of depressive and anxiety symptoms in RA patients, a Plutchik low correlation coefficient with inadequate serum levels of vitamin D was found. However, in the analysis of covariance, we were able to find that vitamin D levels remain associated with a reduction of suicide ideation. Further studies are needed to identify a risk profile for early psychological interventions to improve the quality of life in RA patients.

Barbeya oleoides Leaves Extracts: In Vitro Carbohydrate Digestive Enzymes Inhibition and Phytochemical Characterization.

This study investigated the in vitro inhibitory potential of different solvent extracts of leaves of Barbeya oleoides on key enzymes related to type 2 diabetes mellitus (α-glucosidase and α-amylase) in combination with an aggregation assay (using 0.01% Triton X-100 detergent) to assess the specificity of action. The methanol extract was the most active in inhibiting α-glucosidase and α-amylase, with IC50 values of 6.67 ± 0.30 and 25.62 ± 4.12 µg/mL, respectively. However, these activities were significantly attenuated in the presence of 0.01% Triton X-100. The chemical analysis of the methanol extract was conducted utilizing a dereplication approach combing LC-ESI-MS/MS and database searching. The chemical analysis detected 27 major peaks in the negative ion mode, and 24 phenolic compounds, predominantly tannins and flavonol glycosides derivatives, were tentatively identified. Our data indicate that the enzyme inhibitory activity was probably due to aggregation-based inhibition, perhaps linked to polyphenols.

Meloidogyne enterolobii egg extraction in NaOCl versus infectivity of inoculum on cucumber.

Extraction of eggs of Meloidogyne spp. in sodium hypochlorite (NaOCl) is a helpful procedure to assess the population levels and to obtain inoculum. In this sense, laboratory and greenhouse experiments were done to evaluate the effect of the NaOCl concentration on the viability of M. enterolobii eggs. Additionally, the objective of this investigation was to corroborate the preferable treatments to count populations in cucumber galled roots or to obtain inoculum of M. enterolobii. It was shown that the effect of the NaOCl concentration on the viability of M. enterolobii eggs is potentially detrimental. The NaOCl concentration caused a higher hatching, which in turn, resulted in non-infective larvae. Therefore, the best treatments to obtain inoculum of eggs of M. enterolobii included the 0.75% NaOCl (with 8-min stirring), 0.5% NaOCl (with stirring for 8, 12, and 16 min), and 0.3% NaOCl concentration (with stirring for 8, 12, 16, and 20 min). For a correct estimate of the egg population in roots, we show by several treatments that a concentration of 0.5% NaOCl (with stirring for 8, 12, and 16 min) and 0.75% NaOCl (with 8-min stirring) give the highest results.

Strategies for COVID-19 transmission control and mitigation in a psychiatric hospital in Mexico.

In the context of the emerging COVID-19 pandemic, one of the great challenges is to generate effective strategies for the control of nosocomial infections, specifically in psychiatric hospitals with populations considered at risk (older adults or individuals with comorbidities). This article describes the strategies for prevention, containment and treatment of infection transmission implemented during a COVID-19 outbreak that occurred in July 2020 in a psychiatric hospital of the State of Mexico. The population was comprised by women with prolonged hospital stay (mean = 24 years), mostly geriatric (mean = 64 years), with various psychiatric disorders and comorbidities. In total, 19 COVID-19-positive cases were diagnosed, out of which thirteen had mild symptoms and six were asymptomatic. There were no alterations in mental state, psychiatric symptoms or underlying diseases. Algorithms were developed for the management and treatment of suspected/confirmed COVID-19 cases. Finally, the generation of comprehensive strategies, quick and timely actions, as well as adequate management of human resources favoring interdisciplinary work, were deemed to have contributed to contain and mitigate the COVID-19 outbreak, which constitutes a precedent in the psychiatric field with institutionalized patients.

En el contexto de la emergente pandemia de COVID-19, uno de los grandes desafíos es generar estrategias eficaces de control de infecciones nosocomiales, específicamente en hospitales psiquiátricos con población considerada de riesgo (adultos mayores o con comorbilidades). En el presente artículo se describen las estrategias de prevención, contención y tratamiento de contagio, a partir de un brote de COVID-19 ocurrido en julio de 2020 en un hospital psiquiátrico del Estado de México. La población estuvo constituida por mujeres con estancia hospitalaria prolongada (media = 24 años), en su mayoría geriátricas (media = 64 años), con trastornos psiquiátricos diversos y comorbilidades. En total se diagnosticaron 19 casos positivos de COVID-19, de los cuales 13 cursaron con sintomatología leve y seis resultaron asintomáticos. No se presentaron alteraciones en el estado mental, en la sintomatología psiquiátrica ni en las enfermedades de base. Se realizaron algoritmos para el manejo y tratamiento de los casos sospechosos o confirmados de COVID-19. Finalmente, se consideró que la generación de estrategias integrales, acciones rápidas y oportunas, así como una adecuada gestión de recursos humanos favorecedora del trabajo interdisciplinario contribuyeron a contener y mitigar el brote de COVID-19, constituyéndose en un precedente en el ámbito psiquiátrico con pacientes institucionalizadas.

CDrift: An Algorithm to Correct Linear Drift From A Single High-Resolution STEM Image.

In this work, a new method to determine and correct the linear drift for any crystalline orientation in a single-column-resolved high-resolution scanning transmission electron microscopy (HR-STEM) image, which is based on angle measurements in the Fourier space, is presented. This proposal supposes a generalization and the improvement of a previous work that needs the presence of two symmetrical planes in the crystalline orientation to be applicable. Now, a mathematical derivation of the drift effect on two families of asymmetric planes in the reciprocal space is inferred. However, though it was not possible to find an analytical solution for all conditions, a simple formula was derived to calculate the drift effect that is exact for three specific rotation angles. Taking this into account, an iterative algorithm based on successive rotation/drift correction steps is devised to remove drift distortions in HR-STEM images. The procedure has been evaluated using a simulated micrograph of a monoclinic material in an orientation where all the reciprocal lattice vectors are different. The algorithm only needs four iterations to resolve a 15° drift angle in the image.

Metabolomic and Gene Expression Studies Reveal the Diversity, Distribution and Spatial Regulation of the Specialized Metabolism of Yacón (Smallanthus sonchifolius, Asteraceae).

Smallanthus sonchifolius, also known as yacón, is an Andean crop species commercialized for its nutraceutical and medicinal properties. The tuberous roots of yacón accumulate a diverse array of probiotic and bioactive metabolites including fructooligosaccharides and caffeic acid esters. However, the metabolic diversity of yacón remains unexplored, including the site of biosynthesis and accumulation of key metabolite classes. We report herein a multidisciplinary approach involving metabolomics, gene expression and scanning electron microscopy, to provide a comprehensive analysis of the diversity, distribution and spatial regulation of the specialized metabolism in yacón. Our results demonstrate that different metabolic fingerprints and gene expression patterns characterize specific tissues, organs and cultivars of yacón. Manual inspection of mass spectrometry data and molecular networking allowed the tentative identification of 71 metabolites, including undescribed structural analogues of known bioactive compounds. Imaging by scanning electron microscopy revealed the presence of a new type of glandular trichome in yacón bracts, with a distinctive metabolite profile. Furthermore, the high concentration of sesquiterpene lactones in capitate glandular trichomes and the restricted presence of certain flavonoids and caffeic acid esters in underground organs and internal tissues suggests that these metabolites could be involved in protective and ecological functions. This study demonstrates that individual organs and tissues make specific contributions to the highly diverse and specialized metabolome of yacón, which is proving to be a reservoir of previously undescribed molecules of potential significance in human health.

Actively-monitored periodic-poling in thin-film lithium niobate photonic waveguides with ultrahigh nonlinear conversion efficiency of 4600†%W-1cm-2.

Chip-scale implementations of second-order nonlinear optics benefit from increased optical confinement that can lead to nonlinear interaction strengths that are orders of magnitude higher than bulk free-space configurations. Here, we present thin-film-based ultraefficient periodically-poled lithium niobate nonlinear waveguides, leveraging actively-monitored ferroelectric domain reversal engineering and nanophotonic confinement. The devices exhibit up to 4600 %W-1cm-2 conversion efficiency for second-harmonic generation, pumped around 1540 nm. In addition, we measure broadband sum-frequency generation across multiple telecom bands, from 1460 to 1620 nm. As an immediate application of the devices, we use pulses of picojoule-level energy to demonstrate second-harmonic generation with over 10% conversion in a 0.6-mm-long waveguide. Our ultracompact and highly efficient devices address growing demands in integrated-photonic frequency conversion, frequency metrology, atomic physics, and quantum optics, while offering a coherent link between the telecom and visible bands.

Design of a hybrid chalcogenide-glass on lithium-niobate waveguide structure for high-performance cascaded third- and second-order optical nonlinearities.

Dispersion engineering for efficient supercontinuum generation (SCG) is investigated in a hybrid nonlinear photonic platform that allows cascaded third- and second-order optical nonlinearities in transverse-electric (TE) guided modes. The highly nonlinear chalcogenide waveguides enable SCG spanning over 1.25 octaves (from about 1160 nm to more than 2800 nm at 20 dB below maximum power), while the TE polarization attained is compatible with efficient second-harmonic generation in a subsequent thin-film lithium niobate waveguide integrated monolithically on the same chip. A low-energy pump pulsed laser source of only 25 pJ with 250 fs duration, centered at a wavelength of 1550 nm, can achieve such wideband SCG. The design presented is suitable for the f-to-2f carrier-envelope offset detection technique of stabilized optical frequency comb sources.

In vivo evaluation of the genotoxicity and oxidative damage in individuals exposed to 10% hydrogen peroxide whitening strips.

OBJECTIVE: This study assessed the impact of 10% hydrogen peroxide whitening strip exposure on the genotoxicity and oxidative damage by means of the buccal micronucleus cytome assay by counting nuclear abnormalities (NAs) in buccal mucosa and attached gingiva cells and by analyzing in whole saliva the molecule 8-hydroxy-2'-deoxyguanosine (8-OHdG). MATERIALS AND METHODS: The study was conducted on 113 subjects divided into two groups: group 1 or control (n = 53), non-whitening strip exposed, and group 2 (n = 60), whitening strip exposed (Crest® 3D Whitestrips® premium plus, 10% hydrogen peroxide). Oral epithelial cells and whole saliva samples were taken at the beginning and 30 days later for group 1 and immediately before bleaching and 15 and 30 days after the end of the bleaching for group 2. RESULTS: An increased frequency of NAs (p < 0.05) and higher levels of 8-OHdG (p < 0.05) were observed after bleaching exposure. Also, a positive correlation exists between oxidative stress produced by hydrogen peroxide and micronuclei was found. CONCLUSION: Individuals exposed to 10% hydrogen peroxide whitening strips exhibit NAs increased in oral epithelial cells and 8-OHdG in saliva, which is directed related to nuclear and oxidative DNA damage, respectively. CLINICAL SIGNIFICANCE: Hydrogen peroxide is the active agent of tooth whitening and this compound induced DNA damage. Individuals exposed to whitening strips with 10% hydrogen peroxide exhibit increased genotoxic and oxidative damage. Therefore, self-application of bleaching agents should be handled carefully since it could be a risk to human health.