Molecular Fingerprint Detection Using Raman and Infrared Spectroscopy Technologies for Cancer Detection: A Progress Review.

Molecular vibrations play a crucial role in physical chemistry and biochemistry, and Raman and infrared spectroscopy are the two most used techniques for vibrational spectroscopy. These techniques provide unique fingerprints of the molecules in a sample, which can be used to identify the chemical bonds, functional groups, and structures of the molecules. In this review article, recent research and development activities for molecular fingerprint detection using Raman and infrared spectroscopy are discussed, with a focus on identifying specific biomolecules and studying the chemical composition of biological samples for cancer diagnosis applications. The working principle and instrumentation of each technique are also discussed for a better understanding of the analytical versatility of vibrational spectroscopy. Raman spectroscopy is an invaluable tool for studying molecules and their interactions, and its use is likely to continue to grow in the future. Research has demonstrated that Raman spectroscopy is capable of accurately diagnosing various types of cancer, making it a valuable alternative to traditional diagnostic methods such as endoscopy. Infrared spectroscopy can provide complementary information to Raman spectroscopy and detect a wide range of biomolecules at low concentrations, even in complex biological samples. The article concludes with a comparison of the techniques and insights into future directions.

Development, physicochemical evaluation, and in vivo permeation studies of topical formulations containing 0.1% tacrolimus

Abstract The objective of this paper was to develop and evaluate two semi-solid pharmaceutical forms containing 0.1% tacrolimus: cream (CRT01) and gel (GLT01). For the evaluation of physicochemical stability, at times 0, 30, 60 and 90 days, at 23°C and at 40°C, High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC-DAD) was employed. This method was developed and validated for tacrolimus quantification. The occlusivity test and skin permeation assay were also performed, using an animal model (Wistar rats), and the CRT01 and GLT01 were compared to the 0.1% tacrolimus ointment (PFU01) obtained from the University Pharmacy, Federal University of Rio de Janeiro, Brazil. CRT01 and GLT01 presented a homogeneous aspect and consistency adequate for topical products, along with sensory characteristics above PFU01. They also presented adequate physicochemical stability for 90 days and a lower occlusive effect than PFU01 (p<0.05). CRT01 showed greater affinity for the skin when compared to PFU01 and GLT01, with low systemic absorption. The CRT01 semi-solid formulation was considered the most adequate one to treat patients with atopic dermatitis or other dermatologic inflammatory diseases, promoting rational use of tacrolimus

Modulating physicochemical properties of tetrahydropyridine-2-amine BACE1 inhibitors with electron-withdrawing groups: A systematic study.

A common challenge for medicinal chemists is to reduce the pKa of strongly basic groups' conjugate acids into a range that preserves the desired effects, usually potency and/or solubility, but avoids undesired effects like high volume of distribution (Vd), limited membrane permeation, and off-target binding to, notably, the hERG channel and monoamine receptors. We faced this challenge with a 3,4,5,6-tetrahydropyridine-2-amine scaffold harboring an amidine, a key structural component of potential inhibitors of BACE1, the rate-limiting enzyme in the production of Aß species that make up amyloid plaques in Alzheimer's disease. In our endeavor to balance potency with desirable properties to achieve brain penetration, we introduced a diverse set of groups in beta position of the amidine that modulate logD, PSA and pKa. Given the synthetic challenge to prepare these highly functionalized warheads, we first developed a design flow including predicted physicochemical parameters which allowed us to select only the most promising candidates for synthesis. For this we evaluated a set of commercial packages to predict physicochemical properties, which can guide medicinal chemists in their endeavors to modulate pKa values of amidine and amine bases.

A comparative physicochemical and pharmacological evaluation of dexamethasone sodium phosphate and betamethasone sodium phosphate mucoadhesive gels for the treatment of oral submucous fibrosis in rats

Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.

Nanocristais de besifloxacino para o tratamento de conjuntivite bacteriana: preparação, caracterização físico-química e toxicidade / Besifloxacin nanocrystals for treating bacterial conjunctivitis: preparation, physicochemical characterization, and toxicity

A conjuntivite bacteriana tem significante impacto na Saúde Pública. Essa infecção representa mais de um terço das doenças oculares relatadas em âmbito global. É uma doença altamente contagiosa causada por variedade de bactérias aeróbias e anaeróbias. Diferentes antibióticos empregados no tratamento dessa doença têm apresentado elevada incidência de resistência bacteriana. Dentre os antibióticos de última geração, destaca-se o besifloxacino, antibiótico de quarta geração da classe das fluoroquinolonas, indicado exclusivamente para uso oftálmico tópico. Entretanto, esse fármaco possui baixa solubilidade em água, diminuindo sua biodisponibilidade. Tendo em vista superar esse desafio, foi proposta abordagem nanotecnológica para o desenvolvimento de nanocristais desse fármaco. A preparação de nanocristais de besifloxacino empregando moagem via úmida em escala reduzida foi promissora empregando tensoativo Povacoat®. O Diâmetro hidrodinâmico médio (DHM) da partícula foi de aproximadamente 550 nm, com índice de polidispersão (IP) menor que 0,2. Esse resultado permitiu aumentar a solubilidade de saturação em aproximadamente duas vezes em relação a matéria-prima, possibilitando aumentar a velocidade de dissolução desse fármaco e melhorar sua biodisponibilidade e segurança. Além disso, foi validado o método para quantificação do besifloxacino por CLAE, apresentando especificidade, linearidade no intervalo de 20 a 80µg/mL (r= 0,9996), precisão por repetibilidade (DPR= 1,20%, 0,84% e 0,39%), precisão intermediária (DPR= 0,94%) e exatidão 99,03%. Estudo de estabilidade acelerado (90 dias) na condição 40°C±2°C/75%UR±5%UR e estudo de estabilidade de acompanhamento (150 dias) na condição: 25°C ± 2°C / 60% UR ± 5% UR evidenciaram a estabilidade do teor no período avaliado. Ainda, a nanossuspensão de besifloxacino 0,6% m/m (nanocristais) na dose máxima (500 mg/kg) e o estabilizante Povacoat® (750 mg/kg) não apresentaram toxicidade em larvas de G. mellonella. A concentração inibitória mínima (CIM) para a formulação inovadora foi de 0,0960 µg/mL e 1,60 µg/mL frente a Staphylococcus aureus e Pseudomonas aeruginosa, respectivamente, confirmando eficácia in vitro

Bacterial conjunctivitis greatly impacts the population's health, presenting more than a third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it presents a high incidence of bacterial resistance to the antibiotics commonly used for treatment. Among the most recent antibiotics, besifloxacin is a fourth-generation fluoroquinolone antibiotic indicated exclusively for topical ophthalmic use. Due to its importance in treating bacterial conjunctivitis and its low solubility in the water, a nanotechnological approach was proposed to develop besifloxacin nanocrystals. The preparation of besifloxacin nanocrystals using small-scale wet milling was promising using Povacoat® surfactant. The particle's average hydrodynamic diameter (DHM) was approximately 550 nm, with a polydispersity index (IP) of less than 0.2. This result increased the saturation solubility approximately two times concerning the raw material, making it possible to increase the dissolution rate of this drug and improve its bioavailability and safety. In addition, the method for quantification of besifloxacin by HPLC was validated, presenting specificity, linearity in the range of 20 to 80µg/mL (r= 0.9996), precision by repeatability (DPR= 1.20%, 0.84% and 0.39%), intermediate precision (DPR= 0.94%) and accuracy 99.03%. Accelerated stability study (90 days) at 40°C±2°C/75%RH±5%RH condition and follow-up stability study (150 days) at 25°C ± 2°C / 60% RH ± condition 5% RH showed the stability of content in the evaluated period. Furthermore, the 0.6% besifloxacin nanosuspension (nanocrystals) at the maximum dose (500 mg/kg) and the Povacoat® stabilizer (750 mg/kg) did not show toxicity in G. mellonella larvae. The minimum inhibitory concentration (MIC) to innovative formulation was 0.0960 µg/mL and e 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy

Avaliação do perfil de microRNAs exossomais em portadores de hipercolesterolemia familial / Evaluation of the profile of exosomal microRNAs in patients with familial hypercholesterolemia

A Hipercolesterolemia Familial (HF) é uma doença hereditária do metabolismo lipídico que causa aos portadores alta incidência de aterosclerose prematura. A HF pode ser diagnosticada clínica e geneticamente, entretanto, apenas cerca de 40% podem ter confirmados pelo diagnostico molecular. Assim, outros sistemas de diagnóstico devem ser avaliados. Ultimamente devido a estabilidade em fluidos biológicos, os exossomos circulantes apresentam grande potencial, pois carreiam um número variado de compostos e são considerados veículos de intercomunicação entre os tecidos. Sabe-se que vários RNAs são carreados nos exossomos, incluindo miRNAs, lncRNA e uma variedade de proteínas. Estes componentes podem ser marcadores de diagnóstico para várias doenças inclusive a HF e suas complicações cardiovasculares. Foram utilizadas amostras de exossomos plasmáticos provenientes de 54 pacientes HF sem uso de estatina por, no mínimo, seis semanas, e 38 indivíduos normolipidêmicos para sequenciamento de miRNAs e estudo da proteômica. Os exossomos foram isolados utilizando dois métodos precipitação química e cromatográfica de exclusão de tamanho e caraterizados utilizando: dispersão de luz dinâmica, Western blotting, rastreamento de nanopartículas (NanoSight), imunomarcação e microscopia eletrônica de transmissão. Os miRNAs e proteínas foram extraídos dos exossomos e analisados por sequenciamento de nova geração e espectrometria de massa, respectivamente. Os dados clínicos, biodemográficos e laboratoriais dos pacientes HF e controles indicaram diferenças significativas esperadas entre os grupos, indicando que foram selecionados adequadamente. A caracterização físico-química dos exossomos mostrou resultados com tamanho de ˜90nm e imunorreação positiva para tetraspaninas. O resultado do sequenciamento identificou acima 2000 miRNAs. Os miR-122- 5p e miR-21-5p apresentaram expressão aumentada no grupo HF (log2FC=1,79 e log2FC=1,27, respectivamente), e o miR-122-5p pós normalização em relação ao controle manteve significativo comparados ao controle (p=0,034). A análise comparativa entre exossomos e plasma total mostrou diferença significativa, pois foram identificadas 239 proteínas (p <0,05) diferentes entre exossomos e plasma. Em exossomos, 17 proteínas foram aumentadas e 21 diminuídas em pacientes com HF em comparação com o controle (p <0,05). Destas, seis proteínas foram mais abundantes em HF e sete proteínas foram menos abundantes em exossomos de pacientes com HF em comparação com o controle. A análise de enriquecimento por bioinformática mostrou que a maior parte dessas moléculas (miRNAs e proteínas) foram relacionadas com metabolismo lipídico, dislipidemia, aterosclerose, doença arterial coronariana, adipogênese. Assim, na busca de novos alvos como potenciais biomarcadores de diagnóstico da HF, nossos resultados da análise integrativa entre os miRNAs e as proteínas exossomais abre novas frentes de pesquisa mais bem direcionadas, para a validação desses miRNAs e proteínas exossomais

Familial Hypercholesterolemia (FH) is an inherited disease of lipid metabolism that causes a high incidence of premature atherosclerosis in patients. FH can be diagnosed clinically and genetically, however, only about 40% can be confirmed by molecular diagnosis. Thus, other diagnostic systems should be evaluated. Lately, due to stability in biological fluids, circulating exosomes have great potential, as they carry a varied number of compounds and are considered vehicles of intercommunication between tissues. Several RNAs are known to be carried on exosomes, including miRNAs, lncRNA, and a variety of proteins. These components can be diagnostic markers for several diseases including FH and its cardiovascular complications. Plasma exosome samples from 54 FH patients without statin use for at least six weeks and 38 normolipidemic individuals were used for miRNA sequencing and proteomics studies. Exosomes were isolated using two methods chemical precipitation and size exclusion chromatography and characterized using: dynamic light scattering, Western blotting, nanoparticle tracking (NanoSight), immunostaining and transmission electron microscopy. MiRNAs and proteins were extracted from exosomes and analyzed by next-generation sequencing and mass spectrometry, respectively. Clinical, biodemographic and laboratory data of FH patients and controls indicated significant expected differences between the groups, indicating that they were appropriately selected. The physicochemical characterization of exosomes showed results with a size of ˜90nm and positive immunoreaction for tetraspanins. The sequencing result identified above 2000 miRNAs. miR-122-5p and miR-21-5p showed increased expression in the FH group (log2FC=1.79 and log2FC=1.27, respectively), and miR122-5p after normalization in relation to the control remained significant compared to the control (p=0.034). The comparative analysis between exosomes and total plasma showed a significant difference, as 239 different proteins (p < 0.05) were identified between exosome and plasma. In exosomes, 17 proteins were increased and 21 decreased in FH patients compared to control (p < 0.05). Of these, six proteins were more abundant in FH and seven proteins were less abundant in exosomes from patients with FH compared to the control. Bioinformatics enrichment analysis showed that most of these molecules (miRNAs and proteins) were related to lipid metabolism, dyslipidemia, atherosclerosis, coronary artery disease, adipogenesis. Thus, in the search for new targets as potential diagnostic biomarkers of FH, our results of the integrative analysis between miRNAs and exosomal proteins opens new and better-directed research fronts for the validation of these miRNAs and exosomal proteins

Innovative pharmaceutical strategies for niclosamide repositioning / Estratégias farmacêuticas inovadoras para o reposicionamento da niclosamida

The antiparasitic niclosamide has shown promising anticancer activity in preclinical studies against several types of cancer, such as colorectal and prostate. Thus, the objective of this work was to develop innovative formulations for the repositioning of niclosamide as an anticancer agent. In chapter I, a critical review of the literature on the physicochemical properties of the drug was carried out, in addition the results of clinical studies against colorectal and prostate cancer. Besides, a review was carried out on studies that developed formulations containing this drug, as well as hypotheses to improve the biopharmaceutical performance of this molecule. In chapter II, the development of solid amorphous dispersion containing niclosamide was carried out. Drug/polymer solutions were acoustic levitated and characterized by synchrotron X-ray light. This set allowed fast, high quality measurements, as well as the identification of niclosamide recrystallization. Plasdone® and Soluplus® demonstrated better properties to form amorphous dispersions, with the latter showing superior solubility enhancement. The study showed that the developed formulation increased the apparent saturation solubility of niclosamide in water by two times. In chapter III the objective was the development, physicochemical characterization and in vitro anticancer activity of a niclosamide nanoemulsion, having HCT-116 cells as a cellular model. Preliminary results indicated Capmul® MCM C8 as the best liquid lipid for the system, but the first nanoemulsions containing this lipid were not stable to justify its usage. On the other hand, Miglyol® 812 indicated to be a suitable liquid lipid for the system. The niclosamide nanoemulsion (~200 nm) with Miglyol® 812 and poloxamer 188 was stable for 56 days, with a monomodal particle size distribution. Cell viability assay against HCT-116 cells demonstrated that niclosamide cytotoxicity is time and concentration dependent. Results herein obtained encourage further research to understand and optimize niclosamide performance as an anticancer drug substance

O antiparasitário niclosamida tem apresentado promissora atividade anticâncer em estudos pré- clínicos contra diversos tipos de câncer, como coloretal e próstata. Assim, o objetivo deste trabalho foi desenvolver formulações inovadoras para o reposicionamento da niclosamida como agente anticâncer. No capítulo I foi realizada revisão crítica da literatura sobre as propriedades físico-químicas do fármaco, além de resultados de estudos clínicos da niclosamida contra câncer de coloretal e de próstata. Além disso, foi feita revisão sobre estudos que desenvolveram formulações contendo esse fármaco, bem como hipóteses para melhorar o desempenho biofarmacêutico dessa molécula. No capítulo II foi realizado o desenvolvimento de dispersão solida amorfa contendo niclosamida. Soluções de fármaco/polímero foram levitadas em levitador acústico e caracterizadas por raios-X de luz síncrotron. Este conjunto permitiu medições rápidas e de alta qualidade, bem como identificação de recristalização da niclosamida. Plasdone® e Soluplus® demonstraram melhores propriedades para formar as dispersões amorfas, com o último apresentando aumento de solubilidade superior. O estudo mostrou que a formulação desenvolvida aumentou em duas vezes a solubilidade aparente de saturação da niclosamida em água. No capítulo III o objetivo foi o desenvolvimento, a caracterização físicoquímica e atividade anticâncer in vitro de uma nanoemulsão de niclosamida, tendo células HCT-116 como modelo celular. Resultados preliminares indicaram o Capmul® MCM C8 como o melhor lipídio líquido para o sistema, mas as primeiras nanoemulsões contendo este lipídio não foram estáveis para justificar seu uso. Por outro lado, Miglyol® 812 indicou ser um lipídio líquido adequado para o sistema. A nanoemulsão de niclosamida (~200 nm) com Miglyol® 812 e poloxâmero 188 foi estável por 56 dias, com distribuição monomodal do tamanho de partícula. O ensaio de viabilidade celular contra células HCT-116 demonstrou que a citoxicidade da niclosamida é dependente do tempo e da concentração. Os resultados aqui obtidos encorajam mais pesquisas para entender e otimizar o desempenho da niclosamida como uma substância anticancerígena

Profiling the physicochemical and solid state properties of edible Tetracarpidium conophorum oil and its admixtures for drug delivery

Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.

Bioavailability of ellagitannins from cambuci (Campomanesia Phaea Berg) in healthy and obese subjects / Avaliação da biodisponibilidade dos elagitaninos de cambuci (Campomanesia phaea Berg) em indivíduos saudáveis e com sobrepeso/obesidade

Cambuci (Campomanesia phaea Berg) is a native fruit of the Atlantic Coastal Forest, belonging to the Myrtaceae family, rich in ellagitannins (ET), proanthocyanidins and other bioactive phenolic compounds (BPCs) related to beneficial effects to human health, such as systemic inflammation and attenuation of insulin resistance. Evidence indicates that the beneficial effects of some BPCs, such as ellagitannins, are associated to their chronic intake and the action of the metabolites produced. Urolithins are the main metabolites produced after consumption from a rich source of ellagitannins. According to the metabolite produced, subjects can be classified into metabotypes (A, B e 0). However, nothing is known about the uptake and metabolism of BPC from cambuci. Thus, the objectives of this study were the physical-chemical characterization of cambuci pulp, identification of BPC profile and the determination of their bioavailability in healthy and overweight/obese subjects. Therefore, subjects (n = 28, being 15 healthy and 13 overweight/obese) consumed cambuci juice, and their respective urines 24 hours after drinking were collected to identify the metabolites of ellagitannins. Cambuci presented high acidity, with pH values of ~ 2.3 and titratable acidity of ~ 1.9 g citric acid equivalents/100 g fresh weight (FW), and solids content of ~7.5 ° Brix, not being characterized as a very sweet fruit. The total phenolic content was ~ 780 mg gallic acid/100 mL juice. The total amount of flavan-3-ols found in the fruit was 45.45 g/kg dry weight (DW) and the main monomers identified were gallocatechin (22.25 g/kg DW) and epigallocatechin gallate (16.48 g/kg DW). The degree of polymerization of flavan3-ol was 32.78, indicating a high intensity of astringency and low bioavailability. Through LC-MS, 26 BPCs were identified, most of them being derived from ellagitannins, and among those identified, telemagrandin II and, pedunculagin. The total ellagic acid content found was ~6.2 mg/g DW, demonstrating that cambuci is a fruit rich in ellagic acid and its derivatives. The 28 volunteers who consumed cambuci juice for the bioavailability assessment were classified, for the first time, into metabotypes according to the type of urolithin produced. Metabotype A was the most prevalent (64.3%), followed by metabotype B (17.9%) and 0 (17.9%). When analyzed according to nutritional status, metabotype A was prevalent in both groups. In conclusion, the BCP profile of cambuci stands out for the presence of ET, such as telemagrandin II and pedunculagin. Due to the high degree of polymerization, no proanthocyanidin metabolites were observed. Metabotype A was the most prevalent in this study population, and nutritional status may not be a determining factor in the type of urolithin produced

O cambuci (Campomanesia phaea Berg), é um fruto nativo da mata Atlântica, pertencente à família das mirtáceas, rico em elagitaninos (ET), proantocianidinas e outros compostos bioativos fenólicos (CBF) que estão associados a vários efeitos biológicos benéficos à saúde humana, tais como atenuação inflamação sistêmica e da resistência à insulina. Evidências apontam que os efeitos benéficos de alguns CBF, como os elagitaninos, estão associados com sua ingestão crônica e à ação dos metabólitos produzidos. As urolitinas são os principais metabólitos produzidos após o consumo de uma fonte rica em elagitaninos. De acordo com o metabólito produzido, os indivíduos podem ser classificados em metabotipos (A, B e 0). No entanto, nada se sabe sobre a absorção e a metabolização dos CBF do cambuci. Desta forma, os objetivos deste trabalho foram a caracterização físico-química da polpa de cambuci, a identificação dos CBF e a avaliação da biodisponibilidade dos polifenóis presentes no suco deste fruto, em seres humanos saudáveis e com sobrepeso/obesidade. Para tanto, os voluntários (n = 28, sendo 15 saudáveis e 13 obesos) consumiram suco de cambuci, e suas respectivas urinas 24 horas, após a ingestão da bebida, foram coletadas para identificação dos metabólitos de elagitaninos. O cambuci apresentou uma alta acidez, com valores de pH de ~2,3 e acidez total titulável de ~1,9 g equivalentes de ácido cítrico/100 g em base úmida (b.u.), e teor de sólidos solúveis de ~7,5 ºBrix, não sendo, portanto, muito ácido. O teor de fenólicos totais encontrado foi ~ 780 mg equivalentes de ácido gálico/100 mL de suco. A quantidade total de flavan-3-ois encontrada na polpa de cambuci foi de 45,45 g/kg em base seca (b.s.) e os principais monômeros identificados foram a galocatequina (22,25 g/kg b.s.) e a epigalocatequina galato (16,48 g/kg b.s.). O grau de polimerização do flavan-3-ol foi de 32,78 indicando uma alta intensidade de adstringência e baixa biodisponibilidade. Através de LCMS foi feita a identificação de 26 CBF, sendo sua grande maioria derivados de elagitaninos, e dentre os identificados podemos destacar telemagrandina II e pedunculagina. O teor de elagitaninos encontrado foi de ~6,2 mg/g (b.s.), demonstrando que o cambuci é um fruto rico em ácido elágico e seus derivados. Os 28 voluntários que consumiram o suco de cambuci para ensaio de biodisponibilidade foram classificados, pela primeira vez, em metabotipos de acordo com o tipo de urolitina produzida. O metabotipo A foi o mais prevalente (64,3%), seguido pelo metabotipo B (17,9%) e 0 (17,9%). Quando analisados de acordo com o estado nutricional, o metabotipo A foi prevalente em ambos os grupos. Conclui-se, portanto, que o perfil de CBF do cambuci se destaca pela presença de ET, tais como telimagrandina II e pedunculagina. Devido ao alto grau de polimerização não foram observados metabólitos de proantocianidinas. O metabotipo A foi o mais prevalente na população deste estudo, e o estado nutricional pode não ser um fator determinante no tipo de urolitina produzida

Nanosecond-resolution photothermal dynamic imaging via MHZ digitization and match filtering.

Photothermal microscopy has enabled highly sensitive label-free imaging of absorbers, from metallic nanoparticles to chemical bonds. Photothermal signals are conventionally detected via modulation of excitation beam and demodulation of probe beam using lock-in amplifier. While convenient, the wealth of thermal dynamics is not revealed. Here, we present a lock-in free, mid-infrared photothermal dynamic imaging (PDI) system by MHz digitization and match filtering at harmonics of modulation frequency. Thermal-dynamic information is acquired at nanosecond resolution within single pulse excitation. Our method not only increases the imaging speed by two orders of magnitude but also obtains four-fold enhancement of signal-to-noise ratio over lock-in counterpart, enabling high-throughput metabolism analysis at single-cell level. Moreover, by harnessing the thermal decay difference between water and biomolecules, water background is effectively separated in mid-infrared PDI of living cells. This ability to nondestructively probe chemically specific photothermal dynamics offers a valuable tool to characterize biological and material specimens.

Composition and microbiological quality of refrigerated raw milk in two seasons of the year in Santa Helena, Western Paraná / Composição e qualidade microbiológica do leite cru refrigerado em duas estações do ano em Santa Helena, oeste do Paraná / Composición y calidad microbiológica de la leche cruda refrigerada en dos estaciones del año en Santa Helena, oeste de Paraná

This study aimed at quantifying the occurrence of proteolytic psychotropic microorganisms and total coliforms in refrigerated raw milk, in addition to assessing the quality through its physical-chemical composition. The samples were collected in 10 dairy farms in the municipality of Santa Helena ­ Western Paraná. Two collections were made, one during the spring and the other during the summer. Samples of refrigerated raw milk were carried out directly from the cooling tank, aseptically, packed in sterile bottles and transported under isothermal conditions (± 4 ºC) to the laboratory where the physical-chemical composition and microbial populations were determined. The levels of fat had great amplitude between the seasons, being higher in the summer, while there was no variation for the contents of protein, lactose, minerals, and non-fat solids. The total coliform count did not differ between seasons. The values obtained for proteolytic psychotropic counts were higher in the summer. A significant positive correlation was found between the total coliform counts, the proteolytic psychotropic counts (r=0.73), the levels of protein (r=0.45), non-fat solids (r=0.45), and minerals (r=0.46). Also, the proteolytic psychotropic counts showed a positive correlation with the cryoscopic index. The milk components met the requirements of NI76. The quality of refrigerated raw milk in the municipality of Santa Helena, Western Paraná was not satisfactory for total coliforms, due to its high incidence, indicating the need for good practices in milking management. Proteolytic psychotropic bacteria presented low proliferation, thus not affecting milk quality.(AU)

O presente estudo teve como objetivo quantificar a ocorrência de microrganismos psicrotróficos proteolíticos e de coliformes totais em leite cru refrigerado além de avaliar a qualidade por meio da sua composição físico-química. As amostras foram coletadas em 10 propriedades leiteiras no município de Santa Helena ­ Oeste do Paraná. Foram realizadas duas coletas, uma durante a primavera e outra no verão. As amostragens do leite cru refrigerado foram realizadas diretamente no tanque de resfriamento, de forma asséptica, acondicionado em frascos esterilizados e transportado sob condições isotérmicas (± 4ºC) ao laboratório onde foram determinadas a composição físico-química e as populações microbianas. Os teores de gordura tiveram grande amplitude entre as estações do ano, sendo superior no verão, enquanto que não houve variação para os teores de proteína, lactose, minerais e sólidos desengordurados. A contagem de coliformes totais não diferiu entre as estações. Os valores obtidos para contagens de psicrotróficos proteolíticos foram superiores no verão. Foi constatada correlação significativa positiva entre as contagens de coliformes totais com as contagens de psicrotróficos proteolíticos (r=0,73) e os teores de proteína (r=0,45), sólidos desengordurados (r=0,45) e minerais (r=0,46). Além disto, as contagens de psicrotróficos proteolíticos apresentaram correlação positiva com o índice crioscópico. Os componentes do leite atenderam as exigências da IN76. A qualidade do leite cru refrigerado no município de Santa Helena, Oeste do Paraná não foi satisfatória em relação aos coliformes totais, devido sua alta incidência, indicando a necessidade de boas práticas no manejo de ordenha. As bactérias psicrotróficas proteolíticas tiveram baixa proliferação, não afetando a qualidade do leite.(AU)

El presente estudio tuvo como objetivo cuantificar la ocurrencia de microorganismos psicrotróficos proteolíticos y de coliformes totales en leche cruda refrigerada, además de evaluar la calidad a través de su composición fisicoquímica. Las muestras fueron recolectadas en 10 granjas lecheras del municipio de Santa Helena ­ Oeste de Paraná. Se realizaron dos colecciones, una en primavera y otra en verano. Las muestras de leche cruda enfriada se realizaron directamente en el tanque de enfriamiento, de forma aséptica, se empacaron en botellas estériles y se transportaron en condiciones isotérmicas (± 4ºC) al laboratorio donde se determinó la composición fisicoquímica y las poblaciones microbianas. Los niveles de grasa tuvieron gran amplitud entre las estaciones, siendo más altos en verano, mientras que no hubo variación para los contenidos de proteínas, lactosa, minerales y sólidos desgrasados. El recuento total de coliformes no difirió entre temporadas. Los valores obtenidos para los recuentos de psicotrópicos proteolíticos fueron mayores en verano. Se encontró una correlación positiva significativa entre los recuentos de coliformes totales y los recuentos de psicrótroficos proteolíticos (r=0.73) y los niveles de proteínas (r=0.45), sólidos desgrasados (r=0.45) y minerales (r=0.46). Además, los recuentos de psicrótroficos proteolíticos mostraron una correlación positiva con el índice crioscópico. Los componentes de la leche cumplieron con los requisitos de IN76. La calidad de la leche cruda refrigerada en el municipio de Santa Helena, Oeste de Paraná no fue satisfactoria en relación a los coliformes totales, debido a su alta incidencia, lo que indica la necesidad de buenas prácticas en el manejo del ordeño. Las bacterias psicrotróficas proteolíticas tuvieron baja proliferación, no afectando la calidad de la leche.(AU)

The influence of calculated physicochemical properties of compounds on their ADMET profiles.

We analyzed the influence of calculated physicochemical properties of more than 20,000 compounds on their P-gp and BCRP mediated efflux, microsomal stability, hERG inhibition, and plasma protein binding. Our goal was to provide guidance for designing compounds with desired pharmacokinetic profiles. Our analysis showed that compounds with ClogP less than 3 and molecular weight less than 400 will have high microsomal stability and low plasma protein binding. Compounds with logD less than 2.2 and/or basic pKa larger than 5.3 are likely to be BCRP substrates and compounds with basic pKa less than 5.2 and/or acidic pKa less than 13.4 are less likely to inhibit hERG. Based on these results, compounds with MW < 400, ClogP < 3, basic pKa < 5.2 and acidic pKa < 13.4 are likely to have good bioavailability and low hERG inhibition.

Physico-chemical interactions of a new rod-coil-rod polymer with liposomal system: Approaches to applications in tryptophan-related therapies.

This work describes the synthesis of the new supramolecular rod-coil-rod polymer, designated as cholesterol-PEO1000-tryptophan (Chl-PEO-Trp), as well as its effects on the physico-chemical properties of phosphatidylcholine (PC)-based liposomes. The molecular interactions between the Chl-PEO-Trp and PC were characterized by HATR-FTIR, DSC, NMR, DLS and zeta (ζ) potential techniques. The Chl-PEO-Trp polymer yield was 75 %. FTIR and DSC data showed that the motion of almost all PC groups was restricted by the polymer, and it promoted a decrease of the trans-gauche isomerization of the PC methylene, restricting the mobility of the hydrophobic region of the liposomes. NMR analyses indicated a Chl-PEO-Trp-induced restriction in the rotation of the PC phosphorus and a discreet increase of the hydrogen mobility of the choline. Despite this increase in the rotation of the choline, DLS and ζ-potential analyses suggested a reorientation of the choline group toward the system surface, which contributed, along with the other physico-chemical effects, to a globally packed membrane arrangement and reduced liposome size. Data described in this work were correlated to possible applications of the Chl-PEO-Trp in its free or PC liposome-loaded forms in the diagnosis and therapy of cancer, SARS caused by coronaviruses, and central nervous system-related diseases.

Nanostructured lipid carrier containing hydroxymethylnitrofurazone: preparation, characterization and in vitro and in vivo evaluation of leishmanicidal activity / Carreador lipídico nanoestruturado contendo hidroximetilnitrofural: preparação, caracterização físico-química e avaliação in vitro e in vivo da atividade leishmanicida

Leishmaniasis, a neglected tropical disease (NTD), is a set of diseases caused by obligatory parasitic protozoa of the genus Leishmania. And it has cutaneous and visceral eishmaniasis as its main forms. Treatment includes pentavalent antimonials. These drugs have several disadvantages, such as the need for parenteral administration, use of high dosages, long duration of treatment, severe toxicity, resistance and variable efficacy. The candidate for hydroxymethylnitrofural drug (NFOH), a prodrug derived from nitrofural, showed high activity in cell cultures infected with Trypanosoma cruzi and less toxicity when compared to nitrofural. Due to its low solubility in water and reduced bioavailability, NFOH has failed the in vivo efficacy tests. Nanostructured drug delivery systems have the potential to overcome these challenges due to their evident advantages: greater therapeutic efficacy, less toxicity, modified drug release and increased gastrointestinal absorption of drugs with low water solubility. The objective of this project will be the preparation and evaluation of the physicochemical characteristics of a nanostructured lipid carrier containing hydroxymethylnitrofural (NLC-NFOH). The NFOH showed the highest solubility in Miglyol® 840 among the tested liquid lipids. For solid lipids, Gelucire® 50/13 and Precirol® ATO5 proved to be more suitable for the solubilization of NFOH. The optimized NLC-NFOH consisted of these three lipids. These lipids were selected using a quick Technobis Crystal 16TM methodology, microscopy and DSC. Different lipid selection tools provided scientific knowledge relevant to the development of NLC. The NLC-NFOH had an average z of 198.6 ± 5.4 nm, a PDI of 0.11 ± 0.01 and a zeta potential of -13.7 ± 0.7 mV. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally. The development of a sensitive bioanalytical method using HPLC and evaluation of some analytical figures of merit for the validation allowed the quantification of NFOH and NF. The bioanalytical method for analysis of NFOH and NF use Zorbax SB-C18, 5µm, (4.6x250mm) HPLC column. The mobile phase was consisted of acetonitrile:water (20:80 v/v) with flow rate of 1.2 ml/min, at UV detection of 370 nm. The linearity of NFOH and NF was found in the range 0.0253.0 µg/ml with a correlation coefficient of r > 0.98. The precision was 2.44 to 13.77% for NFOH and 2.61 to 18.42%; the accuracy was 2.66 to 14.28% for NFOH and 2.09 to 19.06% for NF. The method showed to be suitable for effectively evaluation of NFOH is serum. NLC-NFOH (2.8 mg/kg) was administered to animals by gavage, and the blocking flow of the chylomicrons model was performed with an intraperitoneal injection of cycloheximide. The presence of NFOH in serum was evaluated with and without cycloheximide. The cytotoxicity assay of NLC-NFOH and blank-NLC showed more than 90% viable cells at the maximum concentration used (2560 µM). NFOH and NF were detected at 1h after the gavage of DMSO-NFOH or NLC-NFOH, without the pretreatment with cycloheximide. The concentration found for DMSO-NFOH and NLC-NFOH were 0.0316 and 0.0291 µg/mL, respectively. The NLC presented the NFOH absorption by the lymphatic system, demonstrated by blocking chylomicrons flow

A leishmaniose, uma doença tropical negligenciada (DTN), é um conjunto de doenças causadas por protozoários parasitas obrigatórios do gênero Leishmania. E tem como formas principais a leishmaniose cutânea e visceral. O tratamento inclui antimoniais pentavalentes. Esses fármacos apresentam várias desvantagens, como necessidade de administração parenteral, uso de altas dosagens, longa duração do tratamento, toxicidade grave, resistência e eficácia variável. O candidato ao fármaco hidroximetilnitrofural (NFOH), um pró-fármaco derivado do nitrofural, apresentou alta atividade em culturas de células infectadas pelo Trypanosoma cruzi e menor toxicidade quando comparado ao nitrofural. Devido à sua baixa solubilidade em água e biodisponibilidade reduzida, o NFOH falhou nos testes de eficácia in vivo. Os sistemas nanoestruturados de liberação de fármacos têm potencial para superar esses desafios devido às suas vantagens evidentes: maior eficácia terapêutica, menor toxicidade, liberação modificada do fármaco e aumento da absorção gastrointestinal de fármacos com baixa solubilidade em água. O objetivo deste projeto será a preparação e avaliação das características físico-químicas de um carreador lipídico nanoestruturado contendo hidroximetilnitrofural (NLC-NFOH). O NFOH apresentou a maior solubilidade no Miglyol® 840 entre os lipídios líquidos testados. Para lipídios sólidos, Gelucire® 50/13 e Precirol® ATO5 se mostraram mais adequados para a solubilização de NFOH. O NLC-NFOH otimizado consistiu desses três lipídios. Esses lipídios foram selecionados usando Technobis Crystal 16TM, microscopia e DSC. Diferentes ferramentas de seleção de lipídios forneceram conhecimento científico relevante para o desenvolvimento de NLC. O NLC-NFOH teve z-average de 198,6 ± 5,4 nm, PDI de 0,11 ± 0,01 e potencial zeta de -13,7 ± 0,7 mV. Este estudo permitiu o desenvolvimento por abordagem de Design Space do primeiro NLC-NFOH com potencial para tratar a leishmaniose por via oral. O desenvolvimento de um VIII método bioanalítico sensível utilizando HPLC e a avaliação de algumas figuras analíticas de mérito para a validação permitiram a quantificação de NFOH e NF em soro. O método bioanalítico para análise de NFOH e NF usou coluna de HPLC Zorbax SB-C18, 5 µm, (4,6 x 250 mm). A fase móvel foi constituída por acetonitrila: água (20:80 v / v) com vazão de 1,2 ml / min, com detecção no UV de 370 nm. A linearidade de NFOH e NF foi encontrada na faixa de 0,0253,0 µg / ml com um coeficiente de correlação de r> 0,98. A precisão foi de 2,44 a 13,77% para NFOH e 2,61 a 18,42%; a precisão foi de 2,66 a 14,28% para NFOH e 2,09 a 19,06% para NF. O método mostrou-se adequado para avaliação efetiva do NFOH no soro. NLC-NFOH (2,8 mg / kg) foi administrado aos animais por gavagem, e o modelo de bloqueio do fluxo de quilomícrons foi realizado com injeção intraperitoneal de cicloheximida. A presença de NFOH no soro foi avaliada com e sem cicloheximida. O ensaio de citotoxicidade de NLC-NFOH e brancoNLC mostrou mais de 90% de células viáveis na concentração máxima utilizada (2560 µM). NFOH e NF foram detectados 1h após a gavagem de DMSO-NFOH ou NLC-NFOH, sem o pré-tratamento com cicloheximida. As concentrações encontradas para DMSO-NFOH e NLC-NFOH foram 0,0316 e 0,0291 µg / mL, respectivamente. O NLC apresentou a absorção do NFOH pelo sistema linfático, demonstrada pelo bloqueio do fluxo dos quilomícrons

Influence of Powder-to-Gel Ratio on Physicochemical Properties of a Calcium Silicate Sealer / Influencia de la relación polvo-gel sobre las propiedades fisicoquímicas de un sellador de silicato de calcio

Abstract Differences in liquid-to-powder ratio can affect the properties of calcium silicate-based materials. This study assessed the influence of powder-to-gel ratio on physicochemical properties of NeoMTA Plus. Setting time (minutes), flow (mm and mm²), pH (at different periods), radiopacity (mm Al) and solubility (% mass loss) were evaluated using the consistencies for root repair material (NMTAP-RP; 3 scoops of powder to 2 drops of gel) and root canal sealer (NMTAP-SE; 3 scoops of powder to 3 drops of gel), in comparison to Biodentine cement (BIO) and TotalFill BC sealer (TFBC). Statistical analysis was performed using one-way ANOVA and Tukey tests (α=0.05). BIO had the shortest setting time, followed by NMTAP-RP and NMTAP-SE. TFBC showed the highest setting time and radiopacity. BIO, NMTAP-RP, and NMTAP-SE had similar radiopacity. All materials promoted an alkaline pH. NMTAP-RP/SE presented lower solubility than BIO and TFBC. Regarding the flow, TFBC had the highest values, followed by NMTAP-SE, and NMTAP-RP. BIO had the lowest flow. In conclusion, NMTAP in both powder-to-gel ratios showed high pH and low solubility. The increase in the powder ratio decreased the setting time and flow. These findings are important regarding the proper consistency and work time to clinical application.

Resumen Las diferencias en la proporción líquido/polvo pueden afectar las propiedades de los materiales a base de silicato de calcio. Este estudio evaluó la influencia de la proporción polvo/gel en las propiedades fisicoquímicas del cemento NeoMTA Plus. El tiempo de fraguado (minutos), la fluidez (mm y mm²), el pH (en diferentes períodos), la radiopacidad (mmAl) y la solubilidad (% de pérdida de masa) fueron evaluados utilizando las consistencias para el material de reparación radicular (NMTAP-RP; 3 cucharadas de polvo/2 gotas de gel) y para cemento sellador del conducto radicular (NMTAP-SE; 3 cucharadas de polvo/3 gotas de gel), en comparación con el cemento Biodentine (BIO) y el cemento TotalFill BC (TFBC). El análisis estadístico se realizó utilizando las pruebas ANOVA y Tukey unidireccionales (α=0.05). BIO tuvo el tiempo de fraguado más corto, seguido de NMTAP-RP y NMTAP-SE. TFBC mostró el mayor tiempo de fraguado y radiopacidad. BIO, NMTAP-RP y NMTAP-SE tuvieron una radiopacidad similar. Todos los materiales promovieron un pH alcalino. NMTAP-RP/ SE tuvieron una solubilidad menor que BIO y TFBC. Con respecto a la fluidez, TFBC tuvo los valores más altos, seguido de NMTAP-SE y NMTAP-RP. BIO tuvo la fluidez más baja. En conclusión, NMTAP en la relación polvo/gel mostró un pH alto y una baja solubilidad. El aumento en la proporción de polvo disminuyó el tiempo de fraguado y la fluidez. Estos hallazgos son importantes con respecto a su consistencia y tiempo de trabajo durante la aplicación clínica.

Physical-chemical characterization of fresh shanklish cheese with kefir and turmeric extract (Curcuma longa l. ) / Caracterização físico-química de queijo chancliche fresco adicionado de kefir e extrato de açafrão (Curcuma longa l. ) / Caracterización física y química del queso chancliche fresco añadido con extracto de kefir y azafrán (Curcuma longa l. )

Currently, a large number of consumers seek to include functional foods in their diets, aiming beyond the nutritional value prevent health problems, among these foods are probiotic products and vegetables containing bioactive compounds. The objective of this work was to develop and physical-chemically evaluate fresh Shanklish cheeses with the addition of kefir and turmeric extract in order to develop a functional cheese. Shanklish cheese was manufactured and submitted to three different treatments: with the addition of kefir, turmeric extract and both of them. The results obtained for cheese composition were close to the results found in the literature and the cheeses showed stable pH values during the 21 days of storage at 8ºC. It concluded that the addition of kefir and turmeric extract in Shanklish cheese is a way to develop a functional cheese.(AU)

Atualmente é grande o número de consumidores que buscam incluir alimentos funcionais em suas dietas visando além do valor nutricional a prevenção de problemas de saúde, entre esses alimentos encontram-se os produtos probióticos e os vegetais contendo compostos bioativos. O objetivo deste trabalho foi desenvolver e avaliar físico-quimicamente queijos Chancliche frescos com adição de kefir e extrato de cúrcuma buscando o desenvolvimento de um queijo funcional. Foram fabricados queijos Chancliche e submetidos a três tratamentos diferentes: com adição de kefir, extrato de cúrcuma e ambos. Os resultados obtidos para a composição dos queijos estavam próximos dos resultados encontrados na literatura e os queijos mostraram pH estável durante os 21 dias de armazenamento a 8ºC. Concluiu-se que a adição de kefir e extrato de cúrcuma em queijo Chancliche é uma maneira de desenvolver um queijo funcional.(AU)

Actualmente, una gran cantidad de consumidores buscan incluir alimentos funcionales en sus dietas, apuntando más allá del valor nutricional para prevenir problemas de salud, entre estos alimentos se encuentran los productos probióticos y los vegetales que contienen compuestos bioactivos. El objetivo de este trabajo fue desarrollar y evaluar químicamente quesos Chancliche frescos con la adición de kéfir y extracto de cúrcuma para desarrollar un queso funcional. Los quesos Chancliche fueron elaborados y sometidos a tres tratamientos diferentes: con la adición de kéfir, extracto de cúrcuma y ambos. Los resultados obtenidos para la composición de los quesos estaban cercanos a los resultados encontrados en la literatura y los quesos mostraron pH estable durante los 21 días de almacenamiento a 8ºC. Se concluyó que la adición de kéfir y extracto de cúrcuma en queso Chancliche es una forma de desarrollar un queso funcional.(AU)

Processing factors of pesticide residues in biscuits and their relation to the physicochemical properties of pesticides.

Agricultural commodities are generally consumed as processed food. Therefore, it is indispensable to assess pesticide residues in processed products rather than only in the raw agricultural commodity, in order to approach a more realistic scenario of dietary exposure. Processing factors are important tools for dietary exposure risk assessments. In this study, processing factors for the baking process were derived for 41 pesticides in cereal bran-based biscuits. The raw materials used consisted of wheat, rye, oat, and barley grains with incurred pesticides, which originally was produced for test material for European Union Proficiency Tests. Information on physicochemical properties of pesticides was collected for understanding the fate of pesticides during the baking process. Average processing factors varied between 0.67 and 1.6. Most pesticide residues exhibited a reduction of pesticide residues of less than 24%, which correspond to a processing factor (PF) range between 1 and 0.76, showing resistance to the baking process. However, for polar compounds such as carbendazim and volatile compounds (chlorpyrifos-methyl, malathion, and pirimiphos-methyl) larger reduction rates were observed, up to 33% (PF: 0.67). In general, a prolonged baking time did not significantly affect the PF, because the main degradation process takes place within the first 6 min. However, this was not the case for the highly volatile compounds, highly polar compounds, and compounds of low degradation temperature. These latter were significantly reduced with prolonged baking time, resulting in a reduction rate of up to 95%, which means an almost complete elimination.

Identification of Cancer Biomarkers in Human Body Fluids by Using Enhanced Physicochemical-incorporated Evolutionary Conservation Scheme.

OBJECTIVE: Cancer is one of the most serious diseases affecting human health. Among all current cancer treatments, early diagnosis and control significantly help increase the chances of cure. Detecting cancer biomarkers in body fluids now is attracting more attention within oncologists. In-silico predictions of body fluid-related proteins, which can be served as cancer biomarkers, open a door for labor-intensive and time-consuming biochemical experiments. METHODS: In this work, we propose a novel method for high-throughput identification of cancer biomarkers in human body fluids. We incorporate physicochemical properties into the weighted observed percentages (WOP) and position-specific scoring matrices (PSSM) profiles to enhance their attributes that reflect the evolutionary conservation of the body fluid-related proteins. The least absolute selection and shrinkage operator (LASSO) feature selection strategy is introduced to generate the optimal feature subset. RESULTS: The ten-fold cross-validation results on training datasets demonstrate the accuracy of the proposed model. We also test our proposed method on independent testing datasets and apply it to the identification of potential cancer biomarkers in human body fluids. CONCLUSION: The testing results promise a good generalization capability of our approach.

Comparative investigation of phytochemicals among ten citrus herbs by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and evaluation of their antioxidant properties.

The citrus herbs have proved their important medicinal and nutritional values as medicine-food dual-purpose herbs, functional foods, or medical herbs in China. In this study, phytochemicals and antioxidant activity among ten typical citrus herbs (ethanol extracts) were investigated comprehensively. The major ingredients and their contents were analyzed by high-resolution mass spectrometry, and the differences of typical fragment ions between flavanone-7-O-rutinoside(s) and flavanone-7-O-neohesperidoside(s) were discriminated properly in negative electrospray ionization mode. Total polyphenols, total flavonoids, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and ferric reducing antioxidant power tests were performed, which indicated their beneficial values and antioxidant effects. The medicine-food dual-purpose herbs including Chenpi, Juluo, Daidaihua, Huajuhong, Xiangyuan, and Foshou exhibited antioxidant capacities significantly by decreasing intracellular reactive oxygen species intensity (P < 0.01), enhancing superoxide dismutase, catalase, and glutathione peroxidase activities (P < 0.01) in H2 O2 -induced RIN-m5F cells. Moreover, the functional foods Zhishi, Zhiqiao, and Qingpi showed moderate antioxidant bioactivity, while the medical herb Juhe showed weak antioxidant bioactivity, which were consistent with the multivariate analysis of their major flavonoids. The study provided a new sight for the chemical differentiation and practical application of citrus herbs as medicine-food dual-purpose herbs, functional foods, or medical herbs.

Neuron-Inspired Self-Healing Composites via Dynamic Construction of Polypyrrole-Decorated Carbon Nanotubes for Smart Physiochemical Sensing.

Mimicking human skin's functions to develop intelligent materials have inspired extensive exploration in the design and synthesis of a novel device. However, how to simulate neuron function and integrate highly sensitive, positive perceptions and self-healing into one single material remains a challenge. Here, we prepared a recycled polyurethane (PU) with high tensile strength values (11.37 ± 0.03 MPa), high maximum elongation (1130 ± 11.59%), and high self-healing property (100% for 6 h at 25 °C) and a smart PU composite of polypyrrole-decorated carbon nanotubes with higher sensitivity. The smart composite can not only actively identify physical change such as strain, moisture, and temperature but also proactively detect various chemical environment changes such as acid, alkali, oxidant, and reductant (T: 25-90 °C, ΔR/R0 values were 0.1-1.6; strain: 10-150%, ΔR/R0 values were 2.5-27; 0.01-0.1 mol L-1 oxidant solutions, ΔR/R0 values were 0.66-0.75; 0.01-0.1 mol L-1 reductant solutions, ΔR/R0 values were 0.51-0.65; 0.1-0.5 mol L-1 acid solutions, ΔR/R0 values were 0.54-0.58; and 0.1-0.5 mol L-1 alkali solutions, ΔR/R0 values were 0.42-0.46). More importantly, the signal values of the smart composite can quickly return to the initial values after eliminating physical and chemical stimuli. The abovementioned features of the smart composite, the high physicochemical response, and significant restorability make it potentially possible to apply it in intelligent chemical manufacturing.