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1.
Nature ; 629(8013): 910-918, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38693263

RESUMEN

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.


Asunto(s)
Carcinoma de Células Renales , Exposición a Riesgos Ambientales , Geografía , Neoplasias Renales , Mutágenos , Mutación , Femenino , Humanos , Masculino , Ácidos Aristolóquicos/efectos adversos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/inducido químicamente , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Genoma Humano/genética , Genómica , Hipertensión/epidemiología , Incidencia , Japón/epidemiología , Neoplasias Renales/genética , Neoplasias Renales/epidemiología , Neoplasias Renales/inducido químicamente , Mutágenos/efectos adversos , Obesidad/epidemiología , Factores de Riesgo , Rumanía/epidemiología , Serbia/epidemiología , Tailandia/epidemiología , Fumar Tabaco/efectos adversos , Fumar Tabaco/genética
2.
Proc Natl Acad Sci U S A ; 120(8): e2216479120, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36791109

RESUMEN

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investigated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4 promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Serpinas , Humanos , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Oncogenes , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/genética , Proteómica , Estudios Retrospectivos , Serpinas/genética
3.
Development ; 149(7)2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35356969

RESUMEN

Developing organs are shaped, in part, by physical interaction with their environment in the embryo. In recent years, technical advances in live-cell imaging and material science have greatly expanded our understanding of the mechanical forces driving organ formation. Here, we provide a broad overview of the types of forces generated during embryonic development and then focus on a subset of organs underlying our senses: the eyes, inner ears, nose and skin. The epithelia in these organs emerge from a common origin: the ectoderm germ layer; yet, they arrive at unique and complex forms over developmental time. We discuss exciting recent animal studies that show a crucial role for mechanical forces in, for example, the thickening of sensory placodes, the coiling of the cochlea and the lengthening of hair. Finally, we discuss how microfabricated organoid systems can now provide unprecedented insights into the physical principles of human development.


Asunto(s)
Oído Interno , Fenómenos Mecánicos , Animales , Ectodermo , Embrión de Mamíferos , Sensación
4.
Proc Natl Acad Sci U S A ; 119(25): e2026733119, 2022 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-35709320

RESUMEN

Safeguarding Earth's tree diversity is a conservation priority due to the importance of trees for biodiversity and ecosystem functions and services such as carbon sequestration. Here, we improve the foundation for effective conservation of global tree diversity by analyzing a recently developed database of tree species covering 46,752 species. We quantify range protection and anthropogenic pressures for each species and develop conservation priorities across taxonomic, phylogenetic, and functional diversity dimensions. We also assess the effectiveness of several influential proposed conservation prioritization frameworks to protect the top 17% and top 50% of tree priority areas. We find that an average of 50.2% of a tree species' range occurs in 110-km grid cells without any protected areas (PAs), with 6,377 small-range tree species fully unprotected, and that 83% of tree species experience nonnegligible human pressure across their range on average. Protecting high-priority areas for the top 17% and 50% priority thresholds would increase the average protected proportion of each tree species' range to 65.5% and 82.6%, respectively, leaving many fewer species (2,151 and 2,010) completely unprotected. The priority areas identified for trees match well to the Global 200 Ecoregions framework, revealing that priority areas for trees would in large part also optimize protection for terrestrial biodiversity overall. Based on range estimates for >46,000 tree species, our findings show that a large proportion of tree species receive limited protection by current PAs and are under substantial human pressure. Improved protection of biodiversity overall would also strongly benefit global tree diversity.


Asunto(s)
Efectos Antropogénicos , Biodiversidad , Conservación de los Recursos Naturales , Ecosistema , Árboles , Conservación de los Recursos Naturales/métodos , Humanos , Filogenia , Árboles/clasificación
5.
Lancet ; 402(10400): 451-463, 2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37423228

RESUMEN

BACKGROUND: Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. METHODS: This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786. FINDINGS: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2]; stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3-4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). INTERPRETATION: First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. FUNDING: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Calidad de Vida , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
6.
J Transl Med ; 22(1): 618, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961476

RESUMEN

BACKGROUND: Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. METHODS: We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. RESULTS: Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. CONCLUSIONS: In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.


Asunto(s)
Metilación de ADN , Genoma Humano , Neoplasias , Redes Neurales de la Computación , Humanos , Metilación de ADN/genética , Neoplasias/genética , Neoplasias/sangre , Neoplasias/diagnóstico , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Especificidad de Órganos/genética , Algoritmos
7.
Cytotherapy ; 26(6): 641-648, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38506770

RESUMEN

Ex vivo resting culture is a standard procedure following genome editing in hematopoietic stem and progenitor cells (HSPCs). However, prolonged culture may critically affect cell viability and stem cell function. We investigated whether varying durations of culture resting times impact the engraftment efficiency of human CD34+ HSPCs edited at the BCL11A enhancer, a key regulator in the expression of fetal hemoglobin. We employed electroporation to introduce CRISPR-Cas9 components for BCL11A enhancer editing and compared outcomes with nonelectroporated (NEP) and electroporated-only (EP) control groups. Post-electroporation, we monitored cell viability, death rates, and the frequency of enriched hematopoietic stem cell (HSC) fractions (CD34+CD90+CD45RA- cells) over a 48-hour period. Our findings reveal that while the NEP group showed an increase in cell numbers 24 hours post-electroporation, both EP and BCL11A-edited groups experienced significant cell loss. Although CD34+ cell frequency remained high in all groups for up to 48 hours post-electroporation, the frequency of the HSC-enriched fraction was significantly lower in the EP and edited groups compared to the NEP group. In NBSGW xenograft mouse models, both conditioned with busulfan and nonconditioned, we found that immediate transplantation post-electroporation led to enhanced engraftment without compromising editing efficiency. Human glycophorin A+ (GPA+) red blood cells (RBCs) sorted from bone marrow of all BCL11A edited mice exhibited similar levels of γ-globin expression, regardless of infusion time. Our findings underscore the critical importance of optimizing the culture duration between genome editing and transplantation. Minimizing this interval may significantly enhance engraftment success and minimize cell loss without compromising editing efficiency. These insights offer a pathway to improve the success rates of genome editing in HSPCs, particularly for conditions like sickle cell disease.


Asunto(s)
Edición Génica , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas , Animales , Humanos , Edición Génica/métodos , Ratones , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/citología , Trasplante de Células Madre Hematopoyéticas/métodos , Sistemas CRISPR-Cas/genética , Electroporación/métodos , Xenoinjertos , Supervivencia Celular , Antígenos CD34/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo
8.
Chemistry ; 30(7): e202303703, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37953668

RESUMEN

Thiourea derivatives are in-demand motifs in organic synthesis, medicinal chemistry and material science, yet redox methods for the synthesis that start from safe, simple, inexpensive and readily available feedstocks are scarce. In this article, we disclose the synthesis of these motifs using elemental sulfur and nitromethane as the starting materials. The method harnesses the multi-electron auto-redox property of nitromethane in the presence of sulfur and amines, delivering thiourea products without any added oxidant or reductant. Extension of this reaction to cyclizable amines and/or higher homologues of nitromethane led to a wide range of nitrogen heterocycles and thioamides. Operationally simple, the reactions are scalable, tolerate a wide range of functional groups, and can be employed for the direct functionalization of natural products. Mechanistically, the nitro group was found to act as an oxidant leaving group, being reduced to ammonia whereas sulfur, along with the role of a sulfur building block for the thiocarbonyl group, behaved as a complementary reductant, being oxidized to sulfate.

9.
Langmuir ; 40(15): 8260-8270, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38574288

RESUMEN

The introduction of macroporous structures into three-way catalysts (TWCs) through polymer template-assisted spray drying has attracted attention because of its enhanced gas diffusion and catalytic performance. However, the surface charge effect of polymeric template components has not been investigated to control the structure of the TWC particles during synthesis. Thus, this study investigated the effect of template surface charges on the self-assembly behavior of TWC nanoparticles (NPs) during drying. The self-assembly of TWC NPs and polymer particles with different charges produced a hollow structure, whereas using the same charges generated a porous one. Consequently, the mechanism of particle self-assembly during drying and final structure particle formation is proposed in this study. Here, porous TWC particles demonstrated a faster oxidation of soot particles than that of hollow-structured particles. This occurred as a result of the larger contact area between the catalyst surface and the solid reactant. Our findings propose a fundamental self-assembly mechanism for the formation of different TWC structures, thereby enhancing soot oxidation performance using macroporous structures.

10.
Org Biomol Chem ; 22(6): 1167-1171, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38226902

RESUMEN

Inexpensive sodium sulfide trihydrate was found to promote unprecedented 6e-regio-predefined redox condensation of o-nitroanilines with α-tetralones to benzo[a]phenazines. The method was also successfully extended to acetophenones and higher homologs as reducing partners to provide 2-phenylquinoxalines. Compared to traditional approaches toward benzo[a]phenazine and quinoxaline cores starting with o-phenylenediamines, the present strategy could afford these heterocycles with well-defined regiochemistry based on the structure of starting o-nitroanilines.

11.
BMC Infect Dis ; 24(1): 470, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702614

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Vacunas contra Hepatitis B , Hepatitis B , Vacunación , Humanos , Masculino , Femenino , Adulto , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/prevención & control , Vietnam , Vacunación/estadística & datos numéricos , Vacunación/psicología , Persona de Mediana Edad , Adulto Joven , Adolescente , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/estadística & datos numéricos , Virus de la Hepatitis B/inmunología
12.
J Phys Chem A ; 128(15): 2948-2959, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38597180

RESUMEN

Surface-enhanced Raman spectroscopy (SERS) is a powerful Raman technique that provides high selectivity and sensitivity in analyzing the intermolecular interaction of a target compound adsorbed on the surface of a noble nanomaterial, i.e., silver, gold, or copper. Although copper presents a better SERS enhancement than gold and silver, its oxidation in the air is much easier than that of gold and silver. A mixed material between these metals may potentially improve the SERS signal enhancement in this context. In this work, we evaluated the SERS spectra of pyridine (Py) adsorbed on the copper-silver mixed clusters Ag(8-n)Cun (n = 0-8) using density functional theory (DFT) at the PBE functional. The cc-pVDZ-PP basis set was chosen for Ag and Cu, while the cc-pVDZ basis set was used for C, N, and H atoms. Geometrical and electronic structures of the mixed clusters and the Py adsorption configuration on these clusters were computed. The calculated SERS spectra then revealed the influence of the Ag/Cu mixing ratio on the SERS enhancement. As a result, the substituted copper atoms on the silver cluster turned out to be favorable adsorption sites for Py. Interestingly, when the number of Cu atoms increased from n = 0 (pure Ag8 cluster) to n = 5 (Ag3Cu5 cluster), the ring stretching peak (1590 cm-1) of Py significantly increased from 20 to 120 au and then saturated around this value despite increasing the Cu atom number to 8 (pure Cu8 cluster). This observation was extended for other ligands such as pyrazine and 3H-pyrrole. TD-DFT was then employed to clarify the chemical enhancement mechanism. The results obtained hopefully provide helpful information for the design of analytical sensors with lower costs.

13.
Environ Res ; : 119487, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38917932

RESUMEN

The nutraceutical value, and physicochemical profile as well as anti-inflammatory activity potential of Odonthalia floccose and Odonthalia dentata (red macroalgae) dry biomass were investigated in this study. Proximate composition study results revealed that the dry biomass of O. floccose and O. dentae were found to be as ash: 9.11 & 8.7 g 100 g-1, moisture: 8.24 & 8.1 g 100 g-1, total fat: 6.9 & 7.2 g 100 g-1, protein: 24.52 & 25.6 g 100 g-1, and total carbohydrate/polysaccharides: 53.84 & 48.85 g 100 g-1 of dry weight biomass respectively. Both algae biomass contain considerable quantity of minerals (Fe, Cu, Mg, and Zn). Furthermore, the major saturated fatty acids (6.24 & 5.82 g FAME 100 g-1 of total fat of O. floccose and O. dentate) (ΣFAs) present in the test algae were stearic acid, palmitic acid, and margaric acids. O. floccose and O. dentata also contain remarkable protein composition profile that compiled with considerable quantity of essential and non-essential amino acids. The vitamins such as vitamin A, B1, B2, B3, B6, B9, C, and E of O. floccose and O. dentate biomass were also identified at sufficient quantity level. The swelling capacity (SWC), water holding capacity (WHC), and oil holding capacity (OHC) properties of O. floccose and O. dentate at various temperature conditions (25 and 37 ᵒC) were found to be 8.11 & 7.02 mL g-1 and 8.95 & 7.55 mL g-1, 5.1 & 4.87 and 4.8 & 4.1 mL g-1, as well as 2.11 & 1.81 and 1.96 & 1.89 mL g-1 respectively. Among these two marine red macroalgae samples, the O. dentate showed better anti-inflammatory activity than O. floccose at 150 µg mL-1 dosage. Thus, this O. floccose and O. dentate biomass can be considerable as nutritional supplement and pharmaceutical product development related research.

14.
Environ Res ; 251(Pt 2): 118729, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38492832

RESUMEN

The study was carried out to evaluate the effectiveness of the Aristolochia bracteolata water flower extract-mediated AgNPs synthesis and assess their antimicrobial potential. According to the experimental and analytical results, A. bracteolata flower extract can produce valuable AgNPs. The characteristic features of these AgNPs were assessed with UV-visible spectrophotometer, Fourier transform-infrared spectroscopy, Transmission Electron Microscope, Scanning Electron Microscopy, as well as. Under UV-vis. spectrum results, showed major peak at 430 nm and recorded essential functional groups responsible for reducing, capping, and stabilizing AgNPs by FT-IR analysis. In addition, the size and shape of the synthesized AgNPs were found as 21.11-25.17 nm and spherical/octahedral shape. The A. bracteolata fabricated NPs showed remarkable antimicrobial activity against fish bacterial pathogens (V. parahaemolytics, Serratia sp., B. subtilis, and E. coli) as well as common fungal pathogens (A. niger, C. albicans, A. flavus, and A. terreus) at the quantity of 100 µg mL-1 than positive controls. Nevertheless, it was not effective against human bacterial pathogens. It concludes that AgNPs synthesized from A. bracteolata aqueous flower extract have excellent antimicrobial activity and may have a variety of biomedical applications.


Asunto(s)
Antiinfecciosos , Antioxidantes , Aristolochia , Flores , Nanopartículas del Metal , Extractos Vegetales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Flores/química , Nanopartículas del Metal/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Aristolochia/química , Plata/química , Plata/farmacología , Bacterias/efectos de los fármacos
15.
Ann Vasc Surg ; 100: 15-24, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38110082

RESUMEN

BACKGROUND: The effects of incidental radiation exposure on internal mammary arteries remain unclear. The present study was designed to test the hypothesis by comparing diameter and blood flow of the irradiated and nonirradiated internal mammary arteries, using Duplex ultrasound imaging. METHODS: The study was designed as a single-center, transversal, comparative study. The main outcomes were diameter and volumetric blood flow of the internal mammary arteries. The Wilcoxon rank-sum test was used to assess the differences between the irradiated and nonirradiated internal mammary arteries with regard to the diameter and volumetric blood flow. RESULTS: The diameter (median [interquartile range]) of the irradiated internal mammary arteries (0.170 mm [0.160, 0.180]) was smaller than that of the contralateral nonirradiated ones (0.180 mm [0.170, 0.200], P < 0.0001) and that of the internal mammary arteries in the control group (0.180 mm [0.170, 0.190], P < 0.0001). Similarly, blood flow (median [interquartile range]) of the irradiated internal mammary arteries (52.4 ml/min [37.78, 65.57]) was smaller than that of the contralateral nonirradiated ones (62.7 ml/min [46.87, 84.17], P < 0.0001), as well as of the left (56.7 ml/min [46.88, 72.58], P = 0.02) and the right internal mammary arteries in the control group (61.0 ml/min [47.47, 74.52], P = 0 0.0009). CONCLUSIONS: The data indicate that the irradiated internal mammary arteries in patients with a history of total mastectomy followed by radiotherapy for breast cancer had significantly smaller diameter and blood flow compared to the nonirradiated internal mammary arteries.


Asunto(s)
Neoplasias de la Mama , Arterias Mamarias , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Arterias Mamarias/diagnóstico por imagen , Mastectomía Simple , Mastectomía , Resultado del Tratamiento
16.
Nucleic Acids Res ; 50(18): 10544-10561, 2022 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-36161329

RESUMEN

Since plants are sessile organisms, developmental plasticity in response to environmental stresses is essential for their survival. Upon exposure to drought, lateral root development is suppressed to induce drought tolerance. However, the molecular mechanism by which the development of lateral roots is inhibited by drought is largely unknown. In this study, the auxin signaling repressor IAA15 was identified as a novel substrate of mitogen-activated protein kinases (MPKs) and was shown to suppress lateral root development in response to drought through stabilization by phosphorylation. Both MPK3 and MPK6 directly phosphorylated IAA15 at the Ser-2 and Thr-28 residues. Transgenic plants overexpressing a phospho-mimicking mutant of IAA15 (IAA15DD OX) showed reduced lateral root development due to a higher accumulation of IAA15. In addition, MPK-mediated phosphorylation strongly increased the stability of IAA15 through the inhibition of polyubiquitination. Furthermore, IAA15DD OX plants showed the transcriptional downregulation of two key transcription factors LBD16 and LBD29, responsible for lateral root development. Overall, this study provides the molecular mechanism that explains the significance of the MPK-Aux/IAA module in suppressing lateral root development in response to drought.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Sequías , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Raíces de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
17.
Telemed J E Health ; 30(3): 780-787, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37651184

RESUMEN

Objectives: The objectives of this retrospective study were to analyze telehealth utilization for two specialty care practices: oral medicine (OM) and oral and maxillofacial surgery (OMFS) during the first 2 years of the pandemic, its impact as a new treatment modality and on participating providers, as well as identify the type of patient visit that most readily adopted telehealth. Methods: Retrospective study of patients who sought specialty services, OM and OMFS, at an outpatient clinic in a university health system setting between March 1, 2019, and February 28, 2022. Source data were obtained from Epic, an electronic medical record application. Data were graphed using Tableau and Microsoft Excel software. Statistical analysis was performed utilizing chi-squared test and analysis of variance (ANOVA). Results: OMFS utilized telehealth 12% of the time, and OM 8% of the time. The majority (87%) of telehealth visits were for return patients (RPs). Compared with the first year of the pandemic, there was a decrease in the number of telehealth visits in the second year (p = 0.0001). As of August 2022, new patient (NP) telehealth encounters have largely returned to prepandemic levels (0-1.5%), whereas RP telehealth visits remained at an average level of 11.4% (9.4-12.4%). Surveyed providers consider telehealth as an effective complement to in-person care and will continue its use (4.2/5 Likert scale). Conclusions: Telehealth has become a viable pathway of care for OM and OMFS who previously did not utilize the remote platform to deliver healthcare. As a new treatment modality, telehealth is perceived as impactful in increasing access to specialty care by participating providers. NP visits are now almost completely in person, but telehealth continues for RPs. Ongoing demand for telehealth highlights urgency to develop appropriate standards and effective remote diagnostic/monitoring tools to maximize telehealth's capability to leverage finite health care resources and increase access to specialty care.


Asunto(s)
Cirugía Bucal , Telemedicina , Humanos , Estudios Retrospectivos , Atención a la Salud , Pandemias
18.
Reprod Med Biol ; 23(1): e12587, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38854775

RESUMEN

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

19.
J Environ Sci (China) ; 145: 139-151, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38844315

RESUMEN

Linking meteorology and air pollutants is a key challenge. The study investigated meteorological effects on PM2.5 concentration using the advanced convergent cross mapping method, utilizing hourly PM2.5 concentration and six meteorological factors across eight provinces and cities in Vietnam. Results demonstrated that temperature (ρ = 0.30) and radiation (ρ = 0.30) produced the highest effects, followed by humidity (ρ = 0.28) and wind speed (ρ = 0.24), while pressure (ρ = 0.22) and wind direction (ρ = 0.17) produced the weakest effects on PM2.5 concentration. Comparing the ρ values showed that temperature, wind speed, and wind direction had greater impacts on PM2.5 concentration during the dry season whereas radiation had a more influence during the wet season; Southern stations experienced larger meteorological effects. Temperature, humidity, pressure, and wind direction had both positive and negative influences on PM2.5 concentration, while radiation and wind speed mostly had negative influences. During PM2.5 pollution episodes, there was more contribution of meteorological effects on PM2.5 concentration indicated by ρ values. At contaminated levels, humidity (ρ = 0.45) was the most dominant factor affecting PM2.5 concentration, followed by temperature (ρ = 0.41) and radiation (ρ = 0.40). Pollution episodes were pointed out to be more prevalent under higher humidity, higher pressure, lower temperature, lower radiation, and lower wind speed. The ρ calculation also revealed that lower temperature, lower radiation, and higher humidity greatly accelerated each other under pollution episodes, further enhancing PM2.5 concentration. The findings contributed to the literature on meteorology and air pollution interaction.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ciudades , Monitoreo del Ambiente , Material Particulado , Vietnam , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Conceptos Meteorológicos , Estaciones del Año , Viento
20.
Phys Rev Lett ; 131(5): 050802, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37595240

RESUMEN

We develop an iterative, adaptive frequency sensing protocol based on Ramsey interferometry of a two-level system. Our scheme allows one to estimate unknown frequencies with a high precision from short, finite signals consisting of only a small number of Ramsey fringes. It avoids several issues related to processing of decaying signals and reduces the experimental overhead related to sampling. High precision is achieved by enhancing the Ramsey sequence to prepare with high fidelity both the sensing and readout state and by using an iterative procedure built to mitigate systematic errors when estimating frequencies from Fourier transforms. A comparison with state-of-the-art dynamical decoupling techniques reveals a significant speedup of the frequency estimation without loss of precision.

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