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1.
Artigo em Inglês | MEDLINE | ID: mdl-34129510

RESUMO

Diseases can show different courses of progression even when patients share the same risk factors. Recent studies have revealed that the use of trajectories, the order in which diseases manifest throughout life, can be predictive of the course of progression. In this study, we propose a novel computational method for learning disease trajectories from EHR data. The proposed method consists of three parts: first, we propose an algorithm for extracting trajectories from EHR data; second, three criteria for filtering trajectories; and third, a likelihood function for assessing the risk of developing a set of outcomes given a trajectory set. We applied our methods to extract a set of disease trajectories from Mayo Clinic EHR data and evaluated it internally based on log-likelihood, which can be interpreted as the trajectories' ability to explain the observed (partial) disease progressions. We then externally evaluated the trajectories on EHR data from an independent health system, M Health Fairview. The proposed algorithm extracted a comprehensive set of disease trajectories that can explain the observed outcomes substantially better than competing methods and the proposed filtering criteria selected a small subset of disease trajectories that are highly interpretable and suffered only a minimal (relative 5%) loss of the ability to explain disease progression in both the internal and external validation.

2.
J Hazard Mater ; 415: 125653, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34088177

RESUMO

This research experiment was conducted to investigate the potential of Brevundimonas species IITISM22 to remove mercury by using live biomass of bacterial cells at 298, 308, and 318 K. Characterization of bio-sorbent was done by FT-IR and SEM-EDX. The prime functional groups accountable for binding Hg were OH, -NH2, -CH, -SH and -COO. The deformed bacterial structure was seen after Hg adsorption over the bacterial cell. Influences of different experimental factors, such as pH, temperature, contact time, Hg concentration, and biomass dose was examined. IITISM22 exhibited the highest Hg absorption at pH 6.5, contact time of 4 h, and showed an increased adsorption capacity while increasing the concentration of Hg. Kinetics were recommended by pseudo-second-order for adsorption process and isotherm was adequately defined by the Linear Langmuir isotherm model (KL) = 1.4, 1.2, 0.9 mg/l; (RL) = 0.020, 0.015, 0.013, respectively than Freundlich isotherm model. The Activation energy (Ea) of biosorption calculated were (131.10 KJ/mole) by using Arrhenius equation, and the thermodynamic parameters were ΔG⸰ (-41.03, -16.33, -16.12 KJ/mol), ΔH⸰ (-36.87 KJ/mol) and ΔS⸰ (-194.03 J/mol), respectively. These findings suggest that the removal process was based on chemisorption and the biosorption was exothermic. The result of the current experiment indicated that the IITISM22 could be an authentic biosorbent for Hg detoxification.


Assuntos
Mercúrio , Poluentes Químicos da Água , Adsorção , Biomassa , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
3.
Chemosphere ; 279: 130589, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33894513

RESUMO

This study aimed to assess the role of Solanum lycopersicum and plant growth promoting rhizobacterial (PGPR) strains to remove endosulfan present in the soil. S. lycopersicum was grown in endosulfan amended soil (5, 10, 25, and 50 mg kg-1) inoculated with PGPR strains for 40, 80, and 120 days. The influence of PGPR inoculation on endosulfan accumulation in plant tissues, endosulfan degradation in soil, and plant growth parameters were evaluated. The oxidative stress tolerance was assessed by determining the malondialdehyde formation in S. lycopersicum planted in endosulfan stressed soil inoculated with PGPR strains. The results showed that uptake of endosulfan followed root > shoot pathway in association with a reduction in endosulfan accumulation in inoculated plants as related to un-inoculated plants. Moreover, inoculation of PGPR strains showed a beneficial influence on the degradation of endosulfan, Bacillus sp. PRB101 showed maximum degradation (89% at 5 mg kg-1 of soil) of endosulfan at 120 days after sowing. Furthermore, the content of malondialdehyde was lower in inoculated plants as related to un-inoculated plants. Inoculation of PGPR strains efficiently enhanced plant biomass. The findings showed the effectiveness of PGPR strains to increase the decontamination of endosulfan stressed soil and decline endosulfan concentration in the plant tissues.


Assuntos
Lycopersicon esculentum , Poluentes do Solo , Biodegradação Ambiental , Endossulfano , Raízes de Plantas/química , Solo , Microbiologia do Solo , Poluentes do Solo/análise
4.
Phys Chem Chem Phys ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33889892

RESUMO

Most known two-dimensional materials lack a suitable wide-bandgap, and hydrogenation can be effectively utilized to tune the bandgap of some 2D materials. By employing density functional theory calculations, we investigate the effect of hydrogenation on the electronic and optical properties of a recently reported anisotropic penta-Pt2N4 monolayer. The results show that penta-Pt2N4 is thermally and mechanically stable after hydrogenation and also possesses anisotropic Young's modulus and Poisson's ratio. The electronic property analysis using the hybrid functional reveals that penta-Pt2N4 exhibits a bandgap of 1.10 eV, and the hydrogenation significantly enhances the bandgap to 2.70 eV. Furthermore, the hydrogenated Pt2N4 displays a strong optical absorption of up to 6.45 × 105 cm-1 in the ultraviolet region, and low absorption and low reflectivity in the visible region. Our results strongly suggest that the hydrogenated Pt2N4 has tunable electronic and optical properties for applications as a hole-transport material layer in solar cells in the visible region, and as an ultraviolet detector in the ultraviolet region of the electromagnetic spectrum.

5.
Pathol Res Pract ; 220: 153394, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33706124

RESUMO

OBJECTIVES: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene of non-small cell lung carcinomas (NSCLC) can be targeted by the tyrosine kinase inhibitors. A number of molecular diagnostic platforms are used to detect actionable targets in the exon(s) 18, 19, 20, and 21 of the EGFR gene. The Idylla™ system (Biocartis, Mechelen, Belgium) is a relatively novel technique and is unique in integrating both sample processing and real-time polymerase chain reaction (RT-PCR) in a single cartridge. We sought to conduct this study to compare the turnaround time (TAT) and concordance of Idylla™ system with the conventional RT-PCR and next-generation sequencing (NGS) for EGFR mutation detection. METHODS: In this retrospective analysis, 38 formalin-fixed, paraffin-embedded NSCLC tissue blocks with known NGS results by Ion Torrent™ S5 NGS platform were retested by the RT-PCR and Idylla™ platforms. RESULTS: A total of 15 of 38 (39.4 %) tumors that showed various EGFR mutations by NGS and conventional RT-PCR techniques were subjected to the Idylla™testing. These cases satisfied the specimen adequacy criteria of at least 10 % tumor cells for the testing. The mutations detected by the NGS were also detected by the Idylla™ testing. However, NGS identified additional 3 mutations in 3 cases, involving T709 V (exon 18, n = 1) and V774 M (exon 20, n = 2). The tumors with wild type EGFR on NGS did not have any actionable mutation detected by the Idylla™. Average EGFR testing TAT by Idylla™ was only 7.2 h (4-12 hours), as compared to conventional RT-PCR taking 54 h (31-79 hours) and NGS requiring 10.7 days (7.1-14 days). The actual procedure time by conventional RT-PCR was 24 h, NGS was 6.5 days, and Idylla™ was only 3 h. CONCLUSIONS: In summary, the Idylla™EGFR testing is an efficient, rapid, and fairly simple tool that can be used in the routine molecular laboratory with limited expertise and infrastructure and using the lowest amount of tissue material.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33677667

RESUMO

The contamination of soil by heavy metals such as Hg is growing immensely nowadays. The drawbacks of physicochemical methods in the decontamination of polluted soils resulted in the search for an eco-friendly and cost-effective means in this regard. In this study, a potential Hg-resistant bacterial (IITISM23) strain was investigated for their removal potential of Hg, isolated from Hg-contaminated soil. IITISM23 strain was identified as Morganella sp. (MT062474.1) as it showed 99% similarity to genus Morganella of Gammaproteobacteria based on 16S rRNA gene sequencing. The toxicity experiment confirmed that the strain showed high resistance toward Hg. In low nutrient medium, EC50 (effective concentration) values were 6.8 ppm and minimum effective concentration (MIC) was 7.3 ppm, and in a nutrient-rich medium, EC50 value was 32.29 ppm and MIC value was 34.92 ppm, respectively. In in vitro conditions, IITISM23 showed the removal efficiency (81%) of Hg (II) by the volatilization method in Luria-Bertani (LB) broth. The changes in surface morphology of bacteria upon the supplementation of Hg (II) in broth media were determined by SEM-EDX studies, while the changes in functional groups were studied by FT-IR spectroscopy. The mercury reductase activity was determined by a crude extract of the bacterial strain. The optimal pH and temperature for maximum enzyme activity were 8 and 30oC, with Km of 3.5 µmol/l and Vmax of 0.88 µmol/min, respectively. Also, strain IITISM23 showed resistance toward various antibiotics and other heavy metals like cadmium, lead, arsenic, and zinc. Hence, the application of microbes can be an effective measure in the decontamination of Hg from polluted soils.

7.
Bioresour Technol ; 329: 124937, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33712339

RESUMO

With the increasing popularity of waste to energy conversion, demand for large-scale operation of anaerobic digestors has emerged in the market. However, the process instabilities in anaerobic digestors limit the expansion of facilities to high loading rates. The irregularities in the process can be addressed directly by altering the feedstock characteristics provided an on-hand, robust, and sensitive monitoring device is available. In this context, the bioelectrochemical system has emerged as an excellent tool for monitoring and optimizing the anaerobic process within the reactor. This article reviews the gradual evolution in techniques and approaches for monitoring of anaerobic digestion (AD) process. An analysis of the recently popular biosensing techniques has been done with a focus on the bioelectrochemical monitoring system and its operation mode. A brief attempt to highlight the current challenges in the field of bioelectrochemical process monitoring for AD has also been made, which can be supportive of future research.


Assuntos
Reatores Biológicos , Metano , Anaerobiose
8.
PLoS One ; 16(2): e0247115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596239

RESUMO

The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2. We used the approach on 752 clinical samples in duplicates, amounting to a total of 1536 samples which could be sequenced on a single S4 sequencing flow cell on NovaSeq 6000. Our analysis suggests a high concordance between technical duplicates and a high concordance of detection of SARS-CoV-2 between the COVIDSeq as well as RT-PCR approaches. An in-depth analysis revealed a total of six samples in which COVIDSeq detected SARS-CoV-2 in high confidence which were negative in RT-PCR. Additionally, the assay could detect SARS-CoV-2 in 21 samples and 16 samples which were classified inconclusive and pan-sarbeco positive respectively suggesting that COVIDSeq could be used as a confirmatory test. The sequencing approach also enabled insights into the evolution and genetic epidemiology of the SARS-CoV-2 samples. The samples were classified into a total of 3 clades. This study reports two lineages B.1.112 and B.1.99 for the first time in India. This study also revealed 1,143 unique single nucleotide variants and added a total of 73 novel variants identified for the first time. To the best of our knowledge, this is the first report of the COVIDSeq approach for detection and genetic epidemiology of SARS-CoV-2. Our analysis suggests that COVIDSeq could be a potential high sensitivity assay for the detection of SARS-CoV-2, with an additional advantage of enabling the genetic epidemiology of SARS-CoV-2.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/genética , Genoma Viral/genética , Humanos , Índia/epidemiologia , Epidemiologia Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Pandemias , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Sensibilidade e Especificidade
9.
Ecotoxicol Environ Saf ; 208: 111621, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396141

RESUMO

The study explored the polycyclic aromatic hydrocarbon tolerance of indigenous biosurfactant producing microorganisms. Three bacterial species were isolated from crude oil contaminated sites of Haldia, West Bengal. The three species were screened for biosurfactant production and identified by 16S rRNA sequencing as Brevundimonas sp. IITISM 11, Pseudomonas sp. IITISM 19 and Pseudomonas sp. IITISM 24. The strains showed emulsification activities of 51%, 57% and 63%, respectively. The purified biosurfactants were characterised using FT-IR, GC-MS and NMR spectroscopy and found to have structural similarities to glycolipopeptides, cyclic lipopeptides and glycolipids. The biosurfactants produced were found to be stable under a wide range of temperature (0-100 °C), pH (4-12) and salinity (up to 20% NaCl). Moreover, the strains displayed tolerance to high concentrations (275 mg/L) of anthracene and fluorene and showed a good amount of cell surface hydrophobicity with different hydrocarbons. The study reports the production and characterisation of biosurfactant by Brevundimonas sp. for the first time. Additionally, the kinetic parameters of the bacterial strains grown on up to 300 mg/L concentration of anthracene and fluorene, ranged between 0.0131 and 0.0156 µmax (h-1), while the Ks(mg/L) ranged between 59.28 and 102.66 for Monod's Model. For Haldane-Andrew's model, µmax (h-1) varied between 0.0168 and 0.0198. The inhibition constant was highest for Pseudomonas sp. IITISM 19 on anthracene and Brevundimonas sp. IITISM 11 on fluorene. The findings of the study suggest that indigenous biosurfactant producing strains have tolerance to high PAH concentrations and can be exploited for bioremediation purposes.


Assuntos
Antracenos/metabolismo , Biodegradação Ambiental , Fluorenos/metabolismo , Tensoativos/metabolismo , Antracenos/química , Bactérias/metabolismo , Fluorenos/química , Glicolipídeos , Hidrocarbonetos/metabolismo , Cinética , Petróleo/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pseudomonas/metabolismo , RNA Ribossômico 16S/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química
10.
Environ Sci Pollut Res Int ; 28(20): 25798-25807, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33471306

RESUMO

The contribution of heavy metal to the groundwater pollution index (m-HPI) is dependent on other heavy metals present in it. This contribution may be synergistic or anti-synergistic (antagonistic) depending upon the constituent matrix. Both heavy metal type and its concentration are important. m-HPI, a variant of heavy metal pollution index in water, may be calibrated against USEPA hazard index (HI) using a generic multivariate non-linear regression (MVNLR) model. Excellent correlation may be obtained between HI and m-HPI through optimization of normalized weightage factors of constituent metals that contribute to m-HPI. MVNLR model was employed on groundwater samples of ten sites having different heavy metal matrix. The synergistic/antagonistic contribution of heavy metals to m-HPI was well discernible at each site. This study clearly showed that the individual contribution of a particular heavy metal to pollution index might be altered (enhanced or reduced) in the presence of other heavy metals. A calibrated MVNLR model was successfully used for predicting the hazard index (HI) of water samples.


Assuntos
Água Subterrânea , Metais Pesados , Poluentes Químicos da Água , Monitoramento Ambiental , Poluição Ambiental/análise , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análise
11.
J Assoc Physicians India ; 68(11): 33-36, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33187034

RESUMO

Introduction: India has the highest number of TB (27%) and MDR/RR-TB (24%) cases among the notified TB patients. Xpert MTB/ RIF assay is a fully automated cartridge-based real-time PCR to detect MTB and resistance to rifampicin within two hours using three specific primers and five unique molecular probes to target the rpoB gene. This study was done to detect RR-TB cases and frequency of missing probes, which target mutations in rpoB gene, in the different groups of study population in Sirmaur district of Himachal Pradesh. Methods: All, pulmonary and extrapulmonary specimens, were processed for AFB microscopy and Xpert MTB/RIF assay to diagnose TB and RR-TB. Results: Xpert detected MTBC in 721 patients. Using AFB microscopy, only 284 samples were positive. Of these MTB positive patients, 671 had pulmonary TB and 50 were EPTB cases. Resistance to RIF was detected in 31 (4.29%) cases of which resistance in presumptive tuberculosis group and presumptive drug resistant tuberculosis was 1.51% and 9.30% respectively. Twentyeight (4.17%) PTB cases and three (6%) EP-TB cases were resistant to RIF. The frequency of probe E was highest (77.41%) and mutation combination of probes C and D and E and D was 3.22%. Conclusion: Drug resistance in the MTBC is mainly conferred through point mutations in specific gene targets in the bacterial genome. Molecular assays like Genexpert gives rapid diagnosis and Rifampicin resistance. This study helps to provide baseline data of mutations with in the 81 bp of rpoB gene and stresses the need to further evaluate the mutation patterns in this part of the country.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Farmacorresistência Bacteriana/genética , Humanos , Índia , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Sensibilidade e Especificidade , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
12.
Commun Biol ; 3(1): 683, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33204009

RESUMO

Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

13.
J Hazard Mater ; : 124168, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33158657

RESUMO

Based on density functional theory investigation, we exposed the potential application of hexagonal Sb2C3 nanosheet as highly sensitive material for nitrogen-containing gases (NCGs) NH3, NO2 and NO molecules. Our rigorous simulations show that NH3, NO2 and NO molecules shows physisorption on the Sb2C3 nanosheet via vdW DFT-D3 interactions. The calculations were carried out by considering that the monolayer Sb2C3 as the sensor material modulated with its electrical conductivity when its surface adsorbs the gas molecules for their various orientations and positions. It is also found that the magnetic properties are induced in non-magnetic Sb2C3 nanosheet by adsorption of NO molecule. The interaction of the Sb2C3 nanosheet with the gas molecules is further analysed by the charge density difference (CDD), electrostatic potential (ESP) and Bader charge analysis. Our analysis indicates a strong possibility for the detection of NO2 and NO gas molecules by the Sb2C3 based sensor, due to the associated significant changes in the conductivity and reasonable adsorption energy. Also, in the visible region at T = 300 K, very low recovery times have been found as 431 µs, 785.01 s and 53.8 µs for NH3, NO2 and NO, respectively, which strongly suggest the Sb2C3 nanosheets as a better reversible multi-time gas sensor material towards the NCGs adsorption. We also explored the humidity effect on the NCGs based 2D Sb2C3 sensor material. The current-voltage (I-V) characteristics also confirmed the suitability of 2D Sb2C3 in real-time applications. Overall, present work reveals that the 2D Sb2C3 nanosheets as a promising material for semiconductor-based nano sensors for environmentally hazard pollutants like NCG molecules.

14.
Front Oncol ; 10: 543997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072574

RESUMO

Blood plasma is one of the most widely used samples for cancer biomarker discovery research as well as clinical investigations for diagnostic and therapeutic purposes. However, the plasma proteome is extremely complex due to its wide dynamic range of protein concentrations and the presence of high-abundance proteins. Here we have described an optimized, integrated quantitative proteomics pipeline combining the label-free and multiplexed-labeling-based (iTRAQ and TMT) plasma proteome profiling methods for biomarker discovery, followed by the targeted approaches for validation of the identified potential marker proteins. In this workflow, the targeted quantitation of proteins is carried out by multiple-reaction monitoring (MRM) and parallel-reaction monitoring (PRM) mass spectrometry. Thus, our approach enables both unbiased screenings of biomarkers and their subsequent selective validation in human plasma. The overall procedure takes only ~2 days to complete, including the time for data acquisition (excluding database searching). This protocol is quick, flexible, and eliminates the need for a separate immunoassay-based validation workflow in blood cancer biomarker investigations. We anticipate that this plasma proteomics workflow will help to accelerate the cancer biomarker discovery program and provide a valuable resource to the cancer research community.

15.
Anal Bioanal Chem ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32959111

RESUMO

A large number of scientific works have been published on whole-cell heavy metal biosensing based on optical transduction. The advances in the application of biotechnological tools not only have continuously improved the sensitivity, selectivity, and detection range for biosensors but also have simultaneously unveiled new challenges and restrictions for further improvements. This review highlights selected aspects of whole-cell biosensing of heavy metals using optical transducers. We have focused on the progress in genetic modulation in regulatory and reporter modules of recombinant plasmids that has enabled improvement of biosensor performance. Simultaneously, an attempt has been made to present newer platforms such as microfluidics that have generated promising results and might give a new turn to the optical biosensing field.

16.
Beilstein J Org Chem ; 16: 1740-1753, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765794

RESUMO

A robust transition-metal-free strategy is presented to access novel ß-carboline-tethered benzothiophenone derivatives from 1(3)-formyl-ß-carbolines using elemental sulfur activated by Et3N/DMSO. This expeditious catalyst-free reaction proceeds through the formation of ß-carboline-based 2-nitrochalcones followed by an incorporation of sulfur to generate multifunctional ß-carboline-linked benzothiophenones in good to excellent yields. The synthetic strategy could also be extended towards the synthesis of ß-carboline-linked benzothiophenes. Moreover, the afforded products emerged as promising fluorophores and displayed excellent light-emitting properties with quantum yields (ΦF) up to 47%.

17.
Front Chem ; 8: 477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32656180

RESUMO

The utility of (C6F5)3B(OH2) as catalyst for the simple and environmentally benign synthesis of oligosiloxanes directly from hydrosilanes, is reported. This protocol offers several advantages compared to other methods of synthesizing siloxanes, such as mild reaction conditions, low catalyst loading, and a short reaction time with high yields and purity. The considerable H2O-tolerance of (C6F5)3B(OH2) promoted a catalytic route to disiloxanes which showed >99% conversion of three tertiary silanes, Et3SiH, PhMe2SiH, and Ph3SiH. Preliminary data on the synthesis of unsymmetrical disiloxanes (Si-O-Si') suggests that by modifying the reaction conditions and/or using a 1:1 combination of silane to silanol the cross-product can be favored. Intramolecular reactions of disilyl compounds with catalytic (C6F5)3B(OH2) led to the formation of novel bridged siloxanes, containing a Si-O-Si linkage within a cyclic structure, as the major product. Moreover, the reaction conditions enabled recovery and recycling of the catalyst. The catalyst was re-used 5 times and demonstrated excellent conversion for each substrate at 1.0 mol% catalyst loading. This seemingly simple reaction has a rather complicated mechanism. With the hydrosilane (R3SiH) as the sole starting material, the fate of the reaction largely depends on the creation of silanol (R3SiOH) from R3SiH as these two undergo dehydrocoupling to yield a disiloxane product. Generation of the silanol is based on a modified Piers-Rubinsztajn reaction. Once the silanol has been produced, the mechanism involves a series of competitive reactions with multiple catalytically relevant species involving water, silane, and silanol interacting with the Lewis acid and the favored reaction cycle depends on the concentration of various species in solution.

18.
Alcohol Clin Exp Res ; 44(9): 1842-1851, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32628772

RESUMO

BACKGROUND: Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol (EtOH)-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease. METHODS: Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild-type (WT) and Fut2-deficient littermate mice were subjected to Lieber-DeCarli models of chronic EtOH administration and the chronic-binge EtOH diet (NIAAA model). RESULTS: Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2-deficient mice exacerbates chronic EtOH-induced liver injury, steatosis, and inflammation without affecting EtOH metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2'-fucosyllactose (2'-FL) ameliorates EtOH-induced liver disease in Fut2-deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of EtOH-fed mice. CONCLUSIONS: Intestinal α1-2-fucosylation acts as a host-protective mechanism against EtOH-induced liver disease. 2'-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.

19.
Chembiochem ; 21(23): 3410-3416, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32697857

RESUMO

Peptide nucleic acid (PNA) forms a triple helix with double-stranded RNA (dsRNA) stabilized by a hydrogen-bonding zipper formed by PNA's backbone amides (N-H) interacting with RNA phosphate oxygens. This hydrogen-bonding pattern is enabled by the matching ∼5.7 Šspacing (typical for A-form dsRNA) between PNA's backbone amides and RNA phosphate oxygens. We hypothesized that extending the PNA's backbone by one -CH2 - group might bring the distance between PNA amide groups closer to 7 Å, which is favourable for hydrogen bonding to the B-form dsDNA phosphate oxygens. Extension of the PNA backbone was expected to selectively stabilize PNA-DNA triplexes compared to PNA-RNA. To test this hypothesis, we synthesized triplex-forming PNAs that had the pseudopeptide backbones extended by an additional -CH2 - group in three different positions. Isothermal titration calorimetry measurements of the binding affinity of these extended PNA analogues for the matched dsDNA and dsRNA showed that, contrary to our structural reasoning, extending the PNA backbone at any position had a strong negative effect on triplex stability. Our results suggest that PNAs might have an inherent preference for A-form-like conformations when binding double-stranded nucleic acids. It appears that the original six-atom-long PNA backbone is an almost perfect fit for binding to A-form nucleic acids.

20.
BMC Med Educ ; 20(1): 220, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660478

RESUMO

BACKGROUND: Online courses have broken the boundaries in imparting knowledge. While in western countries e-learning in medical education is well accepted, it is still an upcoming field in low- and middle-income countries like India. Attrition is a major threat to online courses world-wide. The objective of this article is to share the experiences in conducting online cancer screening courses, reasons for attrition and ways to improve retention. METHODS: Online training program in preventive oncology for medical professionals is being conducted since 2017, which is 14-week long with weekly one-hour sessions and specific curriculum for healthcare professionals. Since the retention of participants was a major challenge in all the courses, a short online survey was conducted to identify the reason behind quitting the course and suggestions to improve retention. The data was analyzed in November 2019. RESULTS: Among 614 enrolments, 26% (159/614) refused to attend the course and only 55% (252/455) completed the course successfully. Among the attendees 52% (238/455) were females, 71% (325/455) were from the public sector and 71% (324/455) were non-specialists. The attrition was high among non-specialists 49% (160/324), male participants 57% (124/217) and public sector doctors 52% (170/325). The main reasons for quitting the course were high workload in the health facilities 75% (52/69) and poor internet connectivity 12% (8/69). CONCLUSION: The internet connectivity should be strengthened in all the healthcare centers to facilitate e-learning. A dedicated time-slot should be allotted to the providers for e-learning and updating their knowledge in addition to their routine work.

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