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BACKGROUND: Near-infrared II theranostic agents have gained great momentum in the research field of AD owing to the appealing advantages. Recently, an array of activatable NIR-II fluorescence probes has been developed to specifically monitor pathological targets of AD. Furthermore, various NIR-II-mediated nanomaterials with desirable photothermal and photodynamic properties have demonstrated favorable outcomes in the management of AD. METHODS: We summerized amounts of references and focused on small-molecule probes, nanomaterials, photothermal therapy, and photodynamic therapy based on NIR-II fluorescent imaging for the diagnosis and treatment in AD. In addition, design strategies for NIR-II-triggered theranostics targeting AD are presented, and some prospects are also addressed. RESULTS: NIR-II theranostic agents including small molecular probes and nanoparticles have received the increasing attention for biomedical applications. Meanwhile, most of the theranostic agents exhibited the promising results in animal studies. To our surprise, the multifunctional nanoplatforms also show a great potential in the diagnosis and treatment of AD. CONCLUSIONS: Although NIR-II theranostic agents showed the great potential in diagnosis and treatment of AD, there are still many challenges: 1) Faborable NIR-II fluorohpores are still lacking; 2) Biocompatibility, bioseurity and dosage of NIR-II theranostic agents should be further revealed; 3) New equipment and software associated with NIR-II imaging system should be explored.
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Doença de Alzheimer , Raios Infravermelhos , Nanomedicina Teranóstica , Humanos , Nanomedicina Teranóstica/métodos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , AnimaisRESUMO
Dinitroimidazole (DNI) and dinitropyrazole (DNP), along with their congeners, possess similar molecular structures but exhibit distinct melting points. To analyse and elucidate the fundamental reasons for property differences from the perspective of intermolecular interactions, we proposed a simplified approach named binding energy in clusters (BEC) in computing weak interactions within complex crystal systems. Based on the results of the symmetry-adapted perturbation theory (SAPT) calculations, an approximate estimation of the melting point range can be derived by taking into account the cumulative effect (energy of electrostatic, dispersion and induction terms) and repulsive effect (energy of exchange term) values. We have also proposed a formula for calculating the specific melting point, which indicates that stronger intermolecular interactions have a major impact on the melting point, while the distribution of weak interactions also affects the melting point. This work would provide an effective reference for molecular design and structure-performance analysis.
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The metabolism of exogenous substances is affected by the gut microbiota, and the relationship between them has become a hot topic. However, the mechanisms by which the microbiota regulates drug metabolism have not been clearly defined. This study characterizes the expression profiles of host drug-processing genes (DPGs) in antibiotics-treated rats by using an unbias quantitative RNA-sequencing method and investigates the effects of antibiotics-induced depletion of rat microbiota on the pharmacokinetic behaviors of cytochrome P450s (CYPs) probe drugs, and bile acids metabolism by ultra-performance liquid chromatography-tandem mass spectrometry. Our results show that antibiotics treatments altered the mRNA expressions of 112 DPGs in the liver and jejunum of rats. The mRNA levels of CYP2A1, CYP2C11, CYP2C13, CYP2D, CYP2E1, and CYP3A of CYP family members were significantly downregulated in antibiotics-treated rats. Furthermore, antibiotics treatments also resulted in a significant decrease in the protein expressions and enzyme activities of CYP3A1 and CYP2E1 in rat liver. Pharmacokinetic results showed that, except for tolbutamide, antibiotics treatments significantly altered the pharmacokinetic behaviors of phenacetin, omeprazole, metoprolol, chlorzoxazone, and midazolam. In conclusion, the presence of stable, complex, and diverse gut microbiota plays a significant role in regulating the expression of host DPGs, which could contribute to some individual differences in pharmacokinetics. SIGNIFICANCE STATEMENT: This study investigated how the depletion of rat microbiota by antibiotics treatments influences the expression profiles of host DPGs and the pharmacokinetic behaviors of CYPs probe drugs. Combined with previous studies in germ-free mice, this study will improve the understanding of the role of gut microbiota in drug metabolism and contribute to the understanding of individual differences in the pharmacokinetics of some drugs.
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Citocromo P-450 CYP2E1 , Microbiota , Ratos , Animais , Camundongos , Citocromo P-450 CYP2E1/metabolismo , Antibacterianos , Ratos Sprague-Dawley , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , RNA Mensageiro/metabolismoRESUMO
Achieving site-selectivity and chemoselectivity is enormously challenging for substrates with multi-reactive sites in organic reactions. One kind of model substrates, 5-benzyl-1-(2-halobenzyl)-2-phenyl-1H-pyrazol-3(2H)-ones with six reactive sites were chosen as the examples to probe their intramolecular four kinds of five reactions including C(sp3 )-H arylation, C(sp2 )-H arylation, reductive Heck reaction, and domino Heck reaction/alkylation of aryl C(sp2 )-H bonds through variation of the reaction conditions. Screening of the reaction conditions showed that the different bases controlled the palladium-catalyzed intramolecular site-selectivity and chemoselectivity of the substrates: (i) Cesium carbonate (Cs2 CO3 ) promoted the benzyl C(sp3 )-H arylation of the substrates providing dihydropyrazolo[1,5-b]isoquinolin-2(1H)-ones at 100 °C, and isomerization of the dihydropyrazolo[1,5-b]isoquinolin-2(1H)-ones gave isoquinoline derivatives at a higher temperature (140 °C); (ii) Sodium acetate (NaOAc) mediated the aryl C(sp2 )-H arylation of the substrates affording seven-membered biphenyl N-heterocycles; (iii) Sodium dichloroacetate (Cl2 HCCO2 Na) facilitated occurrence of the reductive Heck reaction of the substrates affording 1H-pyrazolo[5,1-a]isoindol-2(8H)-ones; (iv) Sodium trifluoroacetate (F3 CCO2 Na) assisted performance of the domino Heck reaction/aryl C(sp2 )-H alkylation of the substrates leading to the spiro heterocycles. The 'one substrate - multiple reactions - multiple products' strategy greatly reduces cost, increases diversity of products, provides more opportunity for screening of pharmaceutical molecules, and enriches modern organic synthetic chemistry.
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Currently, surveillance for esophageal squamous cell carcinoma (ESCC) runs a risk of underestimation of early lesions which show absence of iodine staining, with no or only mild histologic changes. The development of molecular markers that indicate risk of progression is thus warranted. We performed whole-exome sequencing on biopsies from two sequential endoscopies of a single esophageal lesion and matching blood samples. There were 27 pairs of age-, gender-, pathologic stage-, and sampling interval-matched progressors and non-progressors identified in a prospective community-based ESCC screening trial. Putative molecular progression markers for ESCC were first evaluated by comparing somatic mutation, copy number alteration (CNA), and mutational signature information among progressors and non-progressors. These markers were then validated with another 24 pairs of matched progressors and non-progressors from the same population using gene alteration status identified by target sequencing and quantitative PCR. Progressors had more somatic mutation and CNA burden, as well as apolipoprotein B mRNA editing catalytic polypeptide-like and age-related signature weights compared with non-progressors. A gene score consisting of somatic NOTCH1 mutation and CDKN2A deletion is predictive of risk of progression in lesions which show absence of iodine staining under endoscopy but have no or only mild dysplasia. This gene score was also validated in an external cohort of matched progressors and non-progressors. Absence of NOTCH1 mutation and presence of CDKN2A deletion are markers of progression in squamous lesions of the esophagus. This gene score would be an ideal indicator for assisting the pathologist in the identification of high-risk individuals who could be potentially 'missed' or subject to a risk underestimation by histologic analysis, and might improve the performance of ESCC surveillance. © 2022 The Pathological Society of Great Britain and Ireland.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Iodo , Carcinoma de Células Escamosas/patologia , Ensaios Clínicos como Assunto , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Humanos , Masculino , Mutação , Estudos Prospectivos , Receptor Notch1/genéticaRESUMO
BACKGROUND AND AIM: The impact of the presence of multiple Lugol-unstained lesions (LULs) in the esophagus on the risk of having severe dysplasia and above (SDA) lesions among asymptomatic individuals is unknown. METHODS: We collected demographic factors, behavioral variables, and features of LULs from 1073 participants who were biopsied at baseline endoscopic screening in a population-based screening trial, and these individuals were followed over a median time of 7 years. Outcome events were defined as SDA identified at screening, at reexamination, or during follow-up. "Multiple LULs" were defined as ≥ 2 LULs found in the entirety of the esophagus. Multivariable logistic regression models were fitted to assess the effect of "multiple LULs" on the cumulative risk of SDA. RESULTS: There were 147 SDA cases in the current study. After adjustment for potential risk factors and endoscopic features of LULs, the presence of "multiple LULs" slightly increased the cumulative risk of having SDA with no statistical significance (adjusted odds ratio [OR] = 1.26; 95% confidence interval [CI] [0.85, 1.88]). Further stratified analysis showed that this association was strong among subjects with small LULs (≤ 5 mm) (adjusted OR = 3.29; 95% CI [1.39, 7.79]). However, no such association was observed in subjects with larger LULs (adjusted OR = 0.99; 95% CI [0.63, 1.55], P interaction = 0.022). CONCLUSIONS: The presence of "multiple small LULs (≤ 5 mm)" in chromoendoscopy indicates a higher cumulative risk of having SDA in the esophagus. We recommend biopsies be taken and surveillance be maintained at a more active level in individuals with relatively small but multiple LULs.
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Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/patologia , Esofagoscopia , Corantes , Fatores de RiscoRESUMO
INTRODUCTION: This study aimed to evaluate the impact of Lugol-unstained lesion (LUL) location on the detection yield, which may help the endoscopist select targets for biopsy. METHODS: We enrolled 1064 subjects who had LULs at the baseline screening of a population-based randomized controlled trial. There were 1166 LULs with recorded location and pathologic diagnosis, and these were used for analysis. The detection rate of severe dysplasia and above (SDA) was calculated as the number of LULs identified as SDA divided by the number of LULs biopsied. Logistic regression with a generalized estimating equation was applied to evaluate the association between the location of a given LUL and the risk of the LUL being SDA. RESULTS: The detection rate of SDA for LULs located in the lower, middle, and upper esophagus increased from 5.9% and 10.9% to 16.7%. LUL location was significantly associated with having SDA (adjusted odds ratio (OR)upper vs. lower = 2.88, 95% confidential interval (CI) = 1.48-5.60; adjusted ORmiddle vs. lower = 1.63, 95% CI = 0.96-2.76), and the association was stronger in subgroups with a family history of esophageal squamous cell carcinoma (ESCC) (adjusted ORupper vs. lower = 9.72, 95% CI = 2.57-36.69; adjusted ORmiddle vs. lower = 3.76, 95% CI = 0.93-15.21). CONCLUSIONS: Our results suggest that more attention should be paid by endoscopists to LULs in the upper and middle esophagus, particularly for individuals with a family history of ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Carcinoma de Células Escamosas/patologia , Lesões Pré-Cancerosas/diagnósticoRESUMO
BACKGROUND: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China. METHODS: We extracted age-specific rate of cancer cases and deaths during 2007-2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007-2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1). RESULTS: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7-4.3%) during 2007-2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3-4.9%), 3.3% (95% CI: 2.6-4.1%), 2.4% (95% CI: 1.4-3.5%), 4.4% (95% CI: 2.5-6.4%), and 3.6% (95% CI: 1.4-5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007-2030, except that uterine cancer deaths and mortality were declined. CONCLUSIONS: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned.
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Carcinoma in Situ , Neoplasias Ovarianas , Neoplasias Vaginais , Feminino , Humanos , China/epidemiologia , EnvelhecimentoRESUMO
BACKGROUND: Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) is a novel lncRNA whose cancer-promoting effect in gastric cancer and nasopharyngeal carcinoma has already been demonstrated. However, its functions in esophageal squamous cell carcinoma (ESCC) remains unknown. LncRNAs can interact with RNA-binding proteins (RBPs) and affect gene expression levels through post-transcriptional regulation. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a widely studied RBP, and sirtuin 1 also known as SIRT1 has been reported to be involved in cancer progression. METHODS: Establishment of in vivo models, HE and immunohistochemistry staining verified the oncogenic effect of HOXC-AS1. The interaction relationship between HOXC-AS1, IGF2BP2 and SIRT1 was verified by RNA pulldown and RNA immunoprecipitation (RIP) assay. Relative expression and stability changes of genes were detected by qPCR and actinomycin D experiments. Finally, the effect of HOXC-AS1-IGF2BP2-SIRT1 axis on ESCC was verified by rescue experiments. RESULTS: HOXC-AS1 is highly expressed in ESCC cells and plays oncogenic effects in vivo. qPCR showed the positive relationship between HOXC-AS1 and SIRT1 following HOXC-AS1 knockdown or overexpression. RNA-pulldown, mass spectrometry and RIP assay demonstrated that IGF2BP2 is an RBP downstream of HOXC-AS1. Then, RIP and qPCR showed that IGF2BP2 could bind to SIRT1 mRNA and knockdown IGF2BP2 resulted in decreased SIRT1 mRNA level. Finally, a series of rescue assay showed that the HOXC-AS1-IGF2BP2-SIRT1 axis can affect the function of ESCC. CONCLUSION: LncRNA HOXC-AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sirtuína 1/genética , Neoplasias Esofágicas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proliferação de Células/genéticaRESUMO
The objective was to explore the clinicopathological features of moderately well-differentiated gastric cancer missed by endoscopy. The clinicopathological data of 88 patients who were diagnosed as moderately well-differentiated gastric cancer by biopsy and pathology from January 2019 to December 2020 in Anyang Tumor Hospital were analyzed retrospectively. The clinicopathological features and immunophenotypic characteristics of these gastric cancers were analyzed together with the literature review. Seventy males and 18 females were included in this study. There were 59 cases of gastritis, 14 cases of ulcer and 15 cases of polyp under endoscope. Based on mucous phenotype, there were 27 gastric cases, 18 intestinal cases, 39 gastrointestinal cases and 4 untyping cases. 54 cases expressed mutant p53 and 34 cases had wild type p53. None of the indicators could yield reliablediagnosis, which requires comprehensive morphological and immunohistochemical analysis by the pathologist. Meanwhile, the clinician should give the patient a systematic treatment plan incuding endoscopy, magnifying endoscopy, NBI, linear endoscopic ultrasound and other examinations. Regardless of the diagnostic criteria, once the pathology suggests a tumor lesion, local resection should be performed first. Additional surgery can be performed if there is submucosal invasion.
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A patient presented with a 5-year history of slowly progressive dysphagia. He had moderately differentiated squamous cell carcinoma in the middle thoracic esophagus and underwent partial esophagogastrostomy 16 years prior. The patient with postoperative anastomotic stenoses was treated with radiotherapy at a total dose of 60 Gy after esophagectomy. Endoscopic submucosal dissection (ESD) was used to treat the recurrent tumor.Clinical specimens were obtained from the ESD and the tumor was pathologically confirmed to be fibrosarcoma.
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OBJECTIVE: To understand the current smart phone addiction tendency (SPAT) in medical university students and relationship with personality traits. METHODS: A cross-sectional study from September 2019 to December 2019 selected medical students from Hubei University of China by cluster sampling. Questionnaires were administered to measure smart phone addiction tendency and personality traits. RESULTS: The prevalence of SPAT among 972 medical students was 24.3%. The prevalence was higher in students from one-child family than those with siblings (28.2% vs. 21.7%), and higher among students from urban families than those from rural ones (29.2% vs. 19.7%).Multivariate logistic regression analysis showed that extraversion and neuroticism were correlated with SPAT, with odds ratio and 95% confidence interval being equal to 1.070 (1.011-1.133) and 0.838 (0.795-0.844), respectively. CONCLUSIONS: The prevalence of SPAT was high in medical college students. Extraversion and neuroticism were risk and protective factors for SPAT. Long duration phone use and a low number of physical workouts predicted high SPAT.
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Estudantes de Medicina , Humanos , Estudos Transversais , Personalidade , Transtorno de Adição à Internet , NeuroticismoRESUMO
Here, we report kinetic studies using electron spin resonance spectroscopy on spin catalysis reactions caused by using graphene belts which were synthesized by a radical coupling method. The results show that σ-type free radical species provide the dominant sites for catalytic activity through the spin-spin interaction, although there are some other influencing factors. The spin catalysis mechanism can be applied both in the oxygen reduction reaction (ORR) and in organic synthesis. The graphene belt spin catalyst shows excellent performance with a high ORR half-wave potential of 0.81â V and long-term stability with almost no loss of activity after 50 000 cycles in alkaline media. It also shows excellent performance in a benzylamine coupling with molecular oxygen to generate the corresponding imine at an average conversion of ≈97.7 % and an average yield of ≈97.9 %. This work opens up a new research direction for understanding aerobic processes in the field of spin catalysis.
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Sugars are natural and environmentally benign substances, which can offer various hydroxyl groups. The understanding of details of the hydroxyl interactions in the hydrophilic groups of sugar-based surfactants, as well as the related properties, is still indistinct. Here, novel d-gluconic acetal surfactants with bicyclic and monocyclic structures in the head group were designed and synthesized. The obtained surfactant with a bicyclic architecture exhibited excellent foamability and a multistimulus-responsive behavior toward foam stabilization. In addition, the control of foamability from defoaming and foaming could be achieved by changing pH values or bubbling gas of CO2/N2. To explore the structural effects such as hydroxyl groups and rigidity of the head group on the properties of sugar-based surfactants, another kind of amphiphilic molecule with various OH- groups and a monocycle in the head group was designed for comparison. These two series of amphiphilic molecules both exhibited good surface activity. However, only the d-gluconic acetal surfactant with a bicyclic structure and a smaller number of OH- groups exhibited excellent foamability. Further studies showed that the foam behaviors were attributed to the conformation and arrangement of the surfactant molecule at the surface layer with the assistance of hydrogen bonds formed by hydroxyl groups and H2O molecules. In addition, the surfactant could provide an environmentally friendly foamer in many potential applications.
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Acetais , Tensoativos , Tensoativos/química , Ligação de Hidrogênio , AçúcaresRESUMO
BACKGROUND: Methylated SDC2 and TFPI2 are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples will facilitate developing more eligible methylation markers. METHODS: CRC samples from TCGA and GEO datasets were divided into three groups, High-methylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Low-methylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location and microsatellite instable were then assessed between the three groups and verified in our custom cohort. RESULTS: Samples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. CONCLUSIONS: The current study revealed that the performance of methylation-based markers might be affected by tumor location, patient age, mutation load and MSI, and these respective sides should be considered when developing new methylation markers for CRC detection.
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Neoplasias Colorretais , Metilação de DNA , Glicoproteínas/genética , Sindecana-2 , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Humanos , Instabilidade de Microssatélites , Mutação , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Sindecana-2/genéticaRESUMO
Great efforts have been made to separate micro/nanoparticles in small-volume specimens, but it is a challenge to achieve the simple, maneuverable and low-cost separation of sub-microliter suspension with large separation distances. By simply adding trace amounts of cations (Mg2+/Ca2+/Na+), we experimentally achieved the size-dependent spontaneous separation of colloidal particles in an evaporating droplet with a volume down to 0.2 µL. The separation distance was at a millimeter level, benefiting the subsequent processing of the specimen. Within only three separating cycles, the mass ratio between particles with diameters of 1.0 µm and 0.1 µm can be effectively increased to 13 times of its initial value. A theoretical analysis indicates that this spontaneous separation is attributed to the size-dependent adsorption between the colloidal particles and the aromatic substrate due to the strong hydrated cation-π interactions.
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Nanopartículas , Sódio , Adsorção , Cátions , SuspensõesRESUMO
Leaf color is one of the key factors involved in determining the processing suitability of tea. It relates to differential accumulation of flavor compounds due to the different metabolic mechanisms. In recent years, photosensitive etiolation or albefaction is an interesting direction in tea research field. However, the molecular mechanism of color formation remains unclear since albino or etiolated mutants have different genetic backgrounds. In this study, wide-target metabolomic and transcriptomic analyses were used to reveal the biological mechanism of leaf etiolation for 'Huangyu', a bud mutant of 'Yinghong 9'. The results indicated that the reduction in the content of chlorophyll and the ratio of chlorophyll to carotenoids might be the biochemical reasons for the etiolation of 'Huangyu' tea leaves, while the content of zeaxanthin was significantly higher. The differentially expressed genes (DEGs) involved in chlorophyll and chloroplast biogenesis were the biomolecular reasons for the formation of green or yellow color in tea leaves. In addition, our results also revealed that the changes of DEGs involved in light-induced proteins and circadian rhythm promoted the adaptation of etiolated tea leaves to light stress. Variant colors of tea leaves indicated different directions in metabolic flux and accumulation of flavor compounds.
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Camellia sinensis , Camellia sinensis/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Perfilação da Expressão Gênica , Clorofila/metabolismo , Chá/química , Transcriptoma , Proteínas de Plantas/metabolismoRESUMO
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, which is caused by multi-factors and characterized by two histopathological hallmarks: amyloid-ß (Aß) plaques and neurofibrillary tangles of Tau proteins. Thus, researchers have been devoting tremendous efforts to developing and designing new molecules for the early diagnosis of AD and curative purposes. Curcumin and its scaffold have fluorescent and photochemical properties. Mounting evidence showed that curcumin scaffold had neuroprotective effects on AD such as anti-amyloidogenic, anti-inflammatory, anti-oxidative and metal chelating. In this review, we summarized different curcumin derivatives and analyzed the in vitro and in vivo results in order to exhibit the applications in AD diagnosis, therapeutic monitoring and therapy. The analysis results showed that, although curcumin and its analogues have some disadvantages such as short wavelength and low bioavailability, these shortcomings can be conquered by modifying the structures. Curcumin scaffold still has the potential to be a multifunctional tool for AD research, including AD diagnosis and therapy.
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Doença de Alzheimer , Curcumina , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Placa Amiloide/metabolismo , Proteínas tau/metabolismoRESUMO
Esophageal carcinoma (EC) is a tremendous threat to human health and life worldwide. Long non-coding RNAs (lncRNAs) have been identified as crucial players in carcinomas including EC. An in-depth understanding on regulatory networks of lncRNAs contributes to the better management of EC. In this text, 2052 lncRNAs and 3240 mRNAs were found to be differentially expressed in 5 EC tumor tissues versus adjacent normal tissues by microarray analysis. Moreover, 297 carcinoma-related genes were screened out according to pathway and disease annotation analyses. In addition, 410 potential lncRNA-mRNA cis-regulation pairs and 395 lncRNA-mRNA trans-regulation pairs were screened out. Among these genes, 14 trans-regulated and 19 cis-regulated genes were found to be related with carcinomas. Additionally, 42 possible lncRNA-mRNA trans-regulation pairs and 26 cis-regulation pairs were found to be related with carcinomas. Also, 4 differentially expressed transcription factors in EC and lncRNAs possibly regulated by these transcription factors were screened out. Moreover, plenty of common upregulated or downregulated lncRNAs and mRNAs in EC were identified by comparative analysis for our microarray outcomes and previous high-throughput data. Furthermore, we demonstrated that ENST00000437781.1 knockdown inhibited cell proliferation and facilitated cell apoptosis by downregulating SIX homeobox 4 (SIX4) and ENST00000524987.1 knockdown had no influence on anoctamin 1 calcium activated chloride channel (ANO1) expression in EC cells. In conclusion, we identified some crucial lncRNAs and genes along with potential regulatory networks of lncRNAs/genes, deepening our understanding on pathogenesis of EC.
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Neoplasias Esofágicas , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante , RNA Mensageiro , Neoplasias Esofágicas/genética , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Fatores de TranscriçãoRESUMO
Chiral phosphoric acid-catalyzed couplings of C-alkynyl N,N'-di-(tert-butoxycarbonyl)-aminals with ß-naphthols led to chiral propargylamines in moderate to high yields with high to excellent enantioselectivity, in which the reactions underwent sequential chiral phosphoric acid-catalyzed inâ situ formation of N-(tert-butoxycarbonyl)-imines (N-Boc-imines) from the aminals, and 1,2-addition of ß-naphthols to the N-Boc-imines. Chiral 1,2-dihydronaphtho[2,1-b]furans and naphtho[2,1-b]furans were prepared with satisfactory results when 10â mol% AgOAc and 20â mol% 2,6-lutidine or 1.2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were added to the resulting chiral propargylamines solution, respectively.