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Transition metal dichalcogenides (TMDs) are quantum confined systems with interesting optoelectronic properties, governed by Coulomb interactions in the monolayer (1L) limit, where strongly bound excitons provide a sensitive probe for many-body interactions. Here, we use two-dimensional electronic spectroscopy (2DES) to investigate many-body interactions and their dynamics in 1L-WS2 at room temperature and with sub-10 fs time resolution. Our data reveal coherent interactions between the strongly detuned A and B exciton states in 1L-WS2. Pronounced ultrafast oscillations of the transient optical response of the B exciton are the signature of a coherent 50 meV coupling and coherent population oscillations between the two exciton states. Supported by microscopic semiconductor Bloch equation simulations, these coherent dynamics are rationalized in terms of Dexter-like interactions. Our work sheds light on the role of coherent exciton couplings and many-body interactions in the ultrafast temporal evolution of spin and valley states in TMDs.
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Ion mobility spectrometry (IMS) is a reliable and sensitive technique for the detection and analysis of compounds at the trace level. Depending on the chemical composition of the sample, compounds may be positively or negatively charged to form different polarity ions and detected in positive or negative polarity of the electric field. In order to detect multiple threats simultaneously with miniaturized devices, using a single detection unit to achieve high resolving power and high sensitivity is important. In this work, a miniaturized drift tube with fast polarity switching capabilities integrated with Fourier deconvolution multiplexing techniques is proposed for the first time as a means to improve the performance of ion mobility spectrometry. The sensitivity and resolving power are improved compared to traditional polarity switching signal averaging data acquisition methods. The displayed device had a high resolving power up to 52 at a drift length of 41 mm and a drift tube voltage of 2 kV. Trinitrotoluene (TNT), methamphetamine (MA), benzene, toluene, methyl tert-butyl ether (MTBE), acetic acid, and methylene chloride were evaluated using the proposed fast polarity switching multiplexing spectrometer and exhibited satisfied performance.
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The resolving power of the drift tube ion mobility spectrometry (IMS) is mainly dependent on the drift length, the drift voltage, the pulse width of an ion gate, and the pressure inside the drift tube. Electrospray ionization (ESI)-IMS is a highly sensitive and reliable technique for the detection and analysis of nonvolatile compounds, and high resolving power is necessary to separate structurally similar compounds. To improve the analytical performance of atmospheric pressure ESI-IMS, the Fourier deconvolution (FD) multiplexing technique is investigated as an effective and convenient means to improve the resolving power as well as the signal-to-noise ratio. By reducing the equivalent ion gate opening width to 5 µs using a typical Tyndall-Powell ion shutter, a high resolving power RP up to 170 can be achieved with a drift length of 12 cm and a drift voltage of 10 kV. Rhodamine 6G (R6G), sodium dodecyl sulfate (SDS), methacycline, oxytetracycline, and ractopamine were evaluated using the FD-ESI-IMS, and mixtures with similar ion mobility can be well separated without prolonging the drift length.
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Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.
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Sistemas de Liberação de Medicamentos , Nanopartículas , RNA Mensageiro , Humanos , RNA Mensageiro/genética , RNA Mensageiro/administração & dosagem , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Vacinas de mRNA , Lipídeos/química , LipossomosRESUMO
BACKGROUND: In Canada, only 15% of patients requiring palliative care receive such services in the year before death. We describe health care utilization patterns among home care users in their last 6 months of life to inform care planning for older people with varying mortality risks and evolving care needs as they decline. METHODS: Using population health administrative data from Ontario, we performed a retrospective cohort study involving home care clients aged 50 years and older who received at least 1 interRAI (Resident Assessment Instrument) Home Care assessment between April 2018 and September 2019. We report the proportion of clients who used acute care, long-term care, and palliative home care services within 6 months of their assessment, stratified by their predicted 6-month mortality risk using a prognostic tool called the Risk Evaluation for Support: Predictions for Elder-life in their Communities Tool (RESPECT) and vital status. RESULTS: The cohort included 247 377 adults, 11.9% of whom died within 6 months of an assessment. Among decedents, 50.6% of those with a RESPECT-estimated median survival of fewer than 3 months received at least 1 nonphysician palliative home care visit before death. This proportion declined to 38.7% and 29.5% among decedents with an estimated median survival between 3 and 6 months and between 6 and 12 months, respectively. INTERPRETATION: Many older adults in Ontario do not receive any palliative home care before death. Prognostic tools such as RESPECT may improve recognition of reduced life expectancies and palliative care needs of individuals in their final years of life.
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Serviços de Assistência Domiciliar , Assistência Terminal , Humanos , Pessoa de Meia-Idade , Idoso , Cuidados Paliativos/métodos , Estudos Retrospectivos , Atenção à Saúde , Ontário/epidemiologia , Assistência Terminal/métodosRESUMO
The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MDA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated integrin/FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis.
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Ácido Litocólico , Simulação de Acoplamento Molecular , Sialiltransferases , Ácido Litocólico/farmacologia , Ácido Litocólico/química , Ácido Litocólico/síntese química , Ácido Litocólico/análogos & derivados , Humanos , Sialiltransferases/antagonistas & inibidores , Sialiltransferases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Sulfatos/química , Sulfatos/farmacologia , Sulfatos/síntese química , Metástase Neoplásica , Ácidos Sulfônicos/farmacologia , Ácidos Sulfônicos/química , Ácidos Sulfônicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Adesão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Paxilina/metabolismo , Paxilina/antagonistas & inibidores , Quinase 1 de Adesão Focal/antagonistas & inibidores , Quinase 1 de Adesão Focal/metabolismo , Descoberta de DrogasRESUMO
Sialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications and diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy and metastasis. Sialyltransferases thus represent emerging targets for the development of small molecule cancer drugs. Herein, we report the inhibitory effects of a recently discovered lithocholic acid derivative FCW393 on sialyltransferase catalytic activity, integrin sialyation, cancer-associated signal transduction, MDA-MB-231 and B16F10 cell migration and invasion, and in in vivo studies, on tumor growth, metastasis, and angiogenesis. FCW393 showed effective and selective inhibition of the sialyltransferases ST6GAL1 (IC50 = 7.8 µM) and ST3GAL3 (IC50 = 9.45 µM) relative to ST3GAL1 (IC50 > 400 µM) and ST8SIA4 (IC50 > 100 µM). FCW393 reduced integrin sialylation in breast cancer and melanoma cells dose-dependently and downregulated proteins associated with the integrin-regulated FAK/paxillin and GEF/Rho/ROCK pathways, and with the VEGF-regulated Akt/NFκB/HIF-1α pathway. FCW393 inhibited cell migration (IC50 = 2.6 µM) and invasion in in vitro experiments, and in in vivo studies of tumor-bearing mice, FCW393 reduced tumor size, angiogenesis, and metastatic potential. Based on its demonstrated selectivity, cell permeability, relatively low cytotoxicity (IC50 = 55 µM), and high efficacy, FCW393 shows promising potential as a small molecule experimental tool compound and a lead for further development of a novel cancer therapeutic.
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Movimento Celular , Sialiltransferases , Sialiltransferases/metabolismo , Sialiltransferases/antagonistas & inibidores , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Metástase Neoplásica , Feminino , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Litocólico/farmacologiaRESUMO
Although neoadjuvant target therapy has been used to treat patients with non-small-cell lung cancer (NSCLC), most of these patients have mutations in the epidermal growth factor receptor (EGFR) gene. Few patients to date have received neoadjuvant target therapy for NSCLC containing variants in genes encoding anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a 51-year-old man with a lung mass in the left lower lobe with enlarged mediastinal lymph nodes. He was diagnosed with NSCLC after needle lung biopsy, with next-generation sequencing showing an echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase (EML4-ALK) fusion variant. The patient received neoadjuvant ensartinib, a second-generation ALK-TKI, for 5 months, followed by successful lobectomy through uniportal video-assisted thoracic surgery and adjuvant ensartinib. To our knowledge, few patients with ALK-positive NSCLC had received neoadjuvant treatment with ensartinib. Findings in this patient may widen indications for neoadjuvant target therapy in the treatment of resectable stage II-IIIA ALK-positive NSCLC.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Inibidores de Proteínas Quinases/farmacologia , Proteínas de Fusão Oncogênica/metabolismoRESUMO
INTRODUCTION: Family/friend caregivers play an essential role in promoting the physical and mental health of older adults in need of care - especially during the COVID-19 pandemic and especially in assisted living (AL) homes, where resident care needs are similarly complex as in long-term care homes but fewer staffing resources and services are available. However, little research is available on caregiver involvement and concerns with care of AL residents prior to and during waves 1 and 2 of the COVID-19 pandemic. This study addressed this important knowledge gap. METHODS: This prospective cohort study used baseline and follow-up online surveys with primary caregivers to AL residents in Western Canada who were 65 years or older and had lived in the AL home for at least 3 months before Mar 1, 2020. Surveys assessed the following outcomes in the 3 months prior to and during waves 1 and 2 of the pandemic: sociodemographics, 5 ways of visiting or communicating with residents, involvement in 16 care tasks, concerns with 9 resident physical/mental health conditions, perceived lack of resident access to 7 care services, and whether caregivers felt well informed and involved with resident care. RESULTS: Based on 386 caregiver responses, in-person visits dropped significantly in wave 1 of the pandemic and so did caregiver involvement in nearly all care tasks. While these rates increased in wave 2, most did not return to pre-pandemic levels. Correspondingly, caregiver concerns (already high before the pandemic) substantially increased in wave 1 and stayed high in wave 2. These were particularly elevated among caregivers who did not feel well informed/involved with resident care. CONCLUSIONS: Restricted in-person visiting disrupted resident care and was associated with worse perceptions of resident health and well-being. Continued caregiver involvement in resident care and communication with caregivers even during lockdowns is key to mitigating these issues.
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COVID-19 , Cuidadores , Humanos , Idoso , Cuidadores/psicologia , COVID-19/epidemiologia , Pandemias , Estudos Prospectivos , Controle de Doenças TransmissíveisRESUMO
BACKGROUND: Empowering adolescent girls is an important component of combating malnutrition in this age group. Because empowerment is multidimensional and context specific, it can be difficult for policymakers and practitioners to target the dimensions of empowerment associated with adolescent girls' nutrition in a particular setting. This study sought to identify the empowerment dimensions significantly associated with married adolescent girls' nutritional status in East Africa; a region where malnutrition and gender inequality stubbornly persist. METHODS: We used cross-sectional Demographic and Health Survey (DHS) data from Ethiopia (2016), Kenya (2014), Tanzania (2015-16) and Uganda (2016) to construct and test theoretically informed structural equation models of the relationship between six dimensions of empowerment and BMI-for-age and haemoglobin levels for married adolescent girls aged 15-19 years. RESULTS: Our models were found to be a good fit for the data. Married adolescent girls' access to information, measured by their education level and mass media use, was directly and positively associated with their BMI-for-age (p < 0.05). Asset ownership, measured by owning a house or land alone or jointly, was directly and positively associated with haemoglobin (p < 0.05) and reduced odds of being moderately to severely anemic. Rejecting justifications for intimate partner violence, a measure of respondents' intrinsic agency, was directly and positively associated with the odds of being overweight or obese. Adolescent girls' level of empowerment across all dimensions had a direct relationship with their country of residence and household wealth. CONCLUSIONS: Our findings suggest that investment in girls' access to information through education and mass/social media and their economic empowerment may be important contributors to their overall empowerment and nutritional status. However, caution is needed as greater autonomy may contribute to increased consumption of unhealthy foods that can contribute to overweight and obesity. Strategies to empower married adolescent girls should be tailored to their specific circumstances. There is an urgent need for better data on adolescent empowerment and health, including increased research into age-, sex- and gender-appropriate empowerment measures and longitudinal data to assess causality. The use of statistical models should be complemented by robust qualitative research to further results interpretation.
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Desnutrição , Estado Nutricional , Feminino , Humanos , Adolescente , Análise de Classes Latentes , Estudos Transversais , Sobrepeso , Tanzânia/epidemiologia , Desnutrição/epidemiologiaRESUMO
The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Vacinas Virais , Antivirais/farmacologia , Antivirais/uso terapêutico , Vacina BNT162 , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Vacinas Virais/uso terapêuticoRESUMO
Areca nut is a popular and addictive food as well as a traditional herbal medicine in many countries. Areca nut contains alkaloids including arecoline, guvacine, and arecaidine, which are the major bioactive compounds in areca products. Areca alkaloids can be carcinogenic, and thus sensitive and specific analytical methods are urgently desired for the identification and quantification of these compounds. High-performance liquid chromatography-based methods are often preferred, but areca alkaloids do not have chromophores, and detection using a traditional UV detector can be difficult. The complexity of areca sample extracts can also lead to the co-elution of peaks leading to poor quantitative performance. We report here high-performance liquid chromatography coupled with an ion mobility spectrometer for sensitive determination of areca alkaloids in various products including areca nut, areca nut products, and herbal oral liquid. An X-Bridge reversed-phase C18 column was used in the experiment and was combined with high-performance liquid chromatography coupled to an ion mobility spectrometer system. A custom-made adjustable post-column splitter acted as an interface between the high-performance liquid chromatography and the ion mobility spectrometer; it also acted as the electrospray ionization source. The mobile phase was methanol and 0.5% ammonium hydroxide. The results demonstrate that the splitter can afford a wide range of split ratios that match the ion mobility spectrometer ionization source while keeping the separation efficiency of high-performance liquid chromatography. Three major alkaloid compounds were then accurately determined using the resulting method without dativization steps. Many coeluted high-performance liquid chromatography peaks are effectively separated in the ion mobility spectrometer dimension, which in turn improved the quantification accuracy.
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Alcaloides , Areca , Areca/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Mobilidade Iônica , Nozes/química , Alcaloides/análiseRESUMO
BACKGROUND: To our knowledge, no population-based studies have examined whether family or friend caregivers of men and women differ in their experience of distress over time. Thus, we aimed to describe, on a population-level and longitudinally, how older men and women care-receivers differed in their health and care needs, compare their caregivers' distress trajectories, and identify factors that contribute to the observed differences. METHODS: This is a population-based, retrospective cohort study using routinely collected data. We examined longitudinally 485,407 community-dwelling Ontario residents, aged over 50 years, who have received at least one Residential Assessment Instrument-Home Care (RAI-HC) assessment between April 2008 and June 2015. Descriptive analyses were performed on the demographic characteristics, health profiles, and care needs of men and women. We also compared their caregivers' baseline and one-year change in distress status. Logistic regressions were performed to examine if the effect of gender on caregiver distress is reduced after controlling for care-receiver's health and functional status as well as their caregiver's kinship and co-residence status. RESULTS: Men (39.5% of our cohort) were frailer, required more care, were mostly cared for by their spouses (52%), and mostly lived with their caregiver (66%). In contrast, women (60.5%) were more likely cared for by their child/child-in-law (60%), less likely to live with caregivers (47%), and received less care. Caregivers of men were more likely to be distressed at baseline (27.7% versus 20.4% of women caregivers) and remain distressed (74.6% versus 69.5%) or become distressed (19.3% versus 14.3%) throughout the year. In logistic regression modelling, the effect of care-receiver's gender on caregiver distress is reduced from an unadjusted odds ratio of 1.49 (95% CI: 1.47-1.51) to 1.17 (95% CI: 1.15-1.19) when care-receiver's health and caregiving factors are controlled for. CONCLUSION: Older men and women differed in health and care needs. Caregivers, especially those caring for men, were often distressed and remained so through time. These results highlight the need for policies that account for the differential care needs and caregiver profiles of men and women in order to offer targetted and appropriate support.
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Cuidadores , Emoções , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos de Coortes , CônjugesRESUMO
Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvß3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.
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Neoplasias Colorretais , Tiroxina , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Receptores ErbB/metabolismo , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/farmacologia , Transdução de Sinais , Terpenos , Tiroxina/análogos & derivadosRESUMO
Because of its simplicity, reliability, and sensitivity, the drift tube ion mobility spectrometer (IMS) has been recognized as the equipment of choice for the on-site monitoring and identification of volatile organic compounds (VOCs). However, the performance of handheld IMS is often limited by the size, weight, and drift voltage, which heavily determine the sensitivity and resolving power that is crucial for the detection and identification of VOCs. In this work, we present a low-cost, miniaturized drift tube ion mobility spectrometer incorporated with a miniaturized UV ionization lamp and a relatively low drift voltage. The sensitivity and resolving power are boosted with the implementation of Fourier deconvolution multiplexing compared to the conventional signal averaging data acquisition method. The drift tube provides a high resolving power of up to 52 at a drift length of 41 mm, 10 mm ID dimensions, and a drift voltage of 1.57 kV. Acetone, benzene, dimethyl methyl phosphonate, methyl salicylate, and acetic acid were evaluated in the developed spectrometer and showed satisfactory performance.
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Compostos Orgânicos Voláteis , Acetona , Benzeno , Reprodutibilidade dos TestesRESUMO
Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell metastasis or colonization has been accumulated over the past decades. In this regard, this review comprehensively discusses the results of studies that have led to the recent discovery and development of sialyltransferase inhibitors, their potential biomedical applications in the treatment of cancer metastasis, and their current limitations and future opportunities.
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Sialiltransferases , Animais , Humanos , NeoplasiasRESUMO
Incorporation of water has been revealed to successfully facilitate visible-light photoredox catalysis of indole leading to increased production of C2-quaternary indolinone. The water-promoted photoreaction of indole under catalyst-free conditions by a household compact fluorescence light was also demonstrated. The antiproliferative activity of the synthesized indolinones was evaluated against three human cancer cell lines.
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Antineoplásicos/farmacologia , Indóis/farmacologia , Luz , Água/química , Antineoplásicos/síntese química , Antineoplásicos/química , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Relação Estrutura-AtividadeRESUMO
In response to no national standard for Gynostemma pentaphyllum, a market survey was carried out, and 17 batches of gypenosides extract and 29 batches of Gypenosides Tablets on the market were collected. With gypenoside A as an index, the TLC qualitative identification and HPLC quantitative evaluation method of gypenosides extract and tablets was established. Based on the determination results of 17 batches of gypenosides extract and 29 batches of Gypenosides Tablets, the quality standards of gypenosides extract and tablets were formulated respectively, so as to give suggestions for improving the quality standards of gypenosides extract and tablets. Compared with the existing ministerial standards, the qualitative identification and quantitative detection of specific components were added, in order to provide scientific basis and suggestions for the revision of the quality standard of gypenosides extract and tablet preparation.
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Gynostemma , Extratos Vegetais , Padrões de Referência , ComprimidosRESUMO
The length of a carbon nanotube is an important dimension that has to be adjusted to the requirements of an experiment or application, e.g., through sorting methods. So far, atomic force microscopy (AFM) has been the method of choice for measuring length distributions, despite being an ex situ method with apparent shortcomings. In this work, we explore analytical ultracentrifugation (AUC) as an in situ method for measuring the length distribution of polymer-wrapped (7, 5) single-walled carbon nanotubes dispersed in toluene. This is an AUC study of nanotubes in nonaqueous media, the preferred media for nanotubes used in device fabrication. In AUC, the temporally and spatially dependent change in optical absorption of a sample is measured under centrifugation. The resulting sedimentation curves can be deconvoluted with a standard data processing procedure (SEDFIT), to yield the sedimentation coefficient distribution. However, the conversion of the sedimentation coefficient distribution into a length distribution is nontrivial and requires finding a suitable model for the nanotube friction coefficient. Also, since AUC is based on optical absorption, it yields a volume distribution and not a number distribution as obtained from AFM reference data. By meeting these challenges and finding a surprisingly simple empirical flexible-chain-like model to describe the sedimentation behavior of one specific chiral structure, we suggest AUC as a viable method for measuring in situ nanotube length distributions of nonaqueous dispersions.
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Nucleic acids, as one kind of significant biomarker, have attracted tremendous attention and exhibited immense values in fundamental studies and clinical applications. In this work, we developed a fluorescent assay for detecting nucleic acids in complex samples based on magnetic microbead (MMB)-assisted catalyzed hairpin assembly (CHA) and a donor donor-acceptor fluorescence resonance energy transfer ("DD-A" FRET) signaling mechanism. Three types of DNA hairpin probes were employed in this system, including Capture, H1 (double FAM-labeled probe as FRET donor), and H2 (TAMRA-labeled probe as FRET acceptor). First, the Captures immobilized on MMBs bound to targets in complex samples, and the sequences in Captures that could trigger catalyzed hairpin assembly (CHA) were exposed. Then, target-enriched MMB complexes were separated and resuspended in the reaction buffer containing H1 and H2. As a result, numerous H1-H2 duplexes were formed during the CHA process, inducing an obvious FRET signal. In contrast, CHA could not be triggered, and the FRET signal was weak, while target was absent. With the aid of magnetic separation and "DD-A" FRET, errors from background interference were effectively eliminated. Importantly, this strategy realized amplified detection in buffer, with detection limits of microRNA as low as 34 pM. Furthermore, this method was successfully applied to detect microRNA-21 in serum and cell culture media. The results showed that our method has the potential for biomedical research and clinical application.