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Thermal quenching (TQ) has been naturally entangling with luminescence since its discovery, and lattice vibration, which is characterized as multiphonon relaxation (MPR), plays a critical role. Considering that MPR may be suppressed under exterior pressure, we have designed a core/shell upconversion luminescence (UCL) system of α-NaYF4:Yb/Ln@ScF3 (Ln = Ho, Er, and Tm) with positive/negative thermal expansion behavior so that positive thermal expansion of the core will be restrained by negative thermal expansion of the shell when heated. This imposed pressure on the crystal lattice of the core suppresses MPR, reduces the amount of energy depleted by TQ, and eventually saves more energy for luminescing, so that anti-TQ or even thermally enhanced UCL is obtained.
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BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Terapia Neoadyuvante/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Quimioradioterapia/métodos , Adulto , Resultado del Tratamiento , Edad de InicioRESUMEN
The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.
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Antibacterianos , Carbolinas , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Carbolinas/farmacología , Carbolinas/química , Carbolinas/síntesis química , Humanos , Relación Estructura-Actividad , Animales , Ratones , Bacterias Grampositivas/efectos de los fármacos , Estructura Molecular , Bacterias Gramnegativas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacosRESUMEN
Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4 to 64 µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.
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The impacts of landscape patterns on river water quality are commonly acknowledged, but understanding the complex processes by which landscape patterns affect water quality is still limited, especially in densely populated urban areas. Exploring the mechanisms through which landscape characteristics influence water quality changes in urbanized rivers will benefit regional water resource protection and landscape-scale resource development and utilization. Utilizing daily water quality monitoring data from rivers in the urbanized area of the Pearl River Delta in 2020, our research employed canonical analysis and partial least squares structural equation modeling (PLS-SEM) to explore the processes and mechanisms of the influence of urbanized river landscape patterns on surface water quality. The results indicated that total nitrogen (TN) was the critical indicator limiting the water quality of rivers in the Pearl River Delta. The landscape composition and configuration indexes exhibited non-linear variations with scale, and the landscape fragmentation was higher closer to the river. Landscape patterns had the most significant influence on water quality under the characteristic scale of a 5.50 km circular buffer zone, and landscape composition dominated the change of water quality of urbanized rivers, among which 30.64% of the percentage patch area of construction (C_PLAND) contributed 46.40% to the explanation rate of water quality change, which was the key landscape index affecting water quality. Moreover, landscape patterns had a higher interpretive rate of 39.29% on water quality in the wet season compared to 36.62% in the dry season. Landscape composition had an indirect negative impact on water quality, with a value of 0.47, by affecting the processes of runoff and nutrient migration driven by human activities, while landscape configuration had an indirect negative impact on water quality, with a value of 0.11. Our research quantified the impacts of landscape patterns driven by human activities on surface water quality and proposed management measures to optimize the allocation of landscape resources in riparian zones of urbanized rivers. The results provide a scientific basis for water quality management and protection in urbanized rivers.
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Given metabolic reprogramming in tumours was a crucial hallmark, several studies have demonstrated its value in the diagnostics and surveillance of malignant tumours. The present study aimed to identify a cluster of metabolism-related genes to construct a prediction model for the prognosis of HCC. Multiple cohorts of HCC cases (466 cases) from public datasets were included in the present analysis. (GEO cohort) After identifying a list of metabolism-related genes associated with prognosis, a risk score based on metabolism-related genes was formulated via the LASSO-Cox and LASSO-pcvl algorithms. According to the risk score, patients were stratified into low- and high-risk groups, and further analysis and validation were accordingly conducted. The results revealed that high-risk patients had a significantly worse 5-year overall survival (OS) than low-risk patients in the GEO cohort. (30.0% vs. 57.8%; hazard ratio [HR], 0.411; 95% confidence interval [95% CI], 0.302-0.651; p < 0.001) This observation was confirmed in the external TCGA-LIHC cohort. (34.5% vs. 54.4%; HR 0.452; 95% CI, 0.299-0.681; p < 0.001) To promote the predictive ability of the model, risk score, age, gender and tumour stage were integrated into a nomogram. According to the results of receiver operating characteristic curves and decision curves analysis, the nomogram score possessed a superior predictive ability than conventional factors, which indicate that the risk score combined with clinicopathological features was able to achieve a robust prediction for OS and improve the individualized clinical decision making of HCC patients. In conclusion, the metabolic genes related to OS were identified and developed a metabolism-based predictive model for HCC. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was approved.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Nomogramas , AlgoritmosRESUMEN
A three-component umpolung cascade coupling reaction of phenols, C60 , and different nucleophiles which includes H2 O, alcohols, triphenylamines and carbazoles was developed. Furthermore, one-pot 1,4-bisphenol coupling on C60 has been realized by this method. This practical protocol features high chemo- and regioselectivity, wide substrate range, easy operation and low cost, thus providing a robust method for the one-pot synthesis of various unsymmetrical 1,4-[60]fullerephenols.
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BACKGROUND: DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC. METHODS: A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis. RESULTS: Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140-3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better. CONCLUSIONS: RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.
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Neoplasias Colorrectales , Humanos , Estadificación de Neoplasias , Neoplasias Colorrectales/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Pronóstico , Metilación de ADN , Carcinogénesis/genética , Transformación Celular Neoplásica/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.
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COVID-19 , Enfermedades Transmisibles , Subtipo H1N1 del Virus de la Influenza A , Infección por el Virus Zika , Virus Zika , Humanos , PrevalenciaRESUMEN
Matched autoproduct processing (MAP) refers to a matched field processing (MFP) style array signal processing technique for passive source localization, which interrogates frequency-difference autoproduct instead of genuine acoustic pressure. Due to frequency downshifting, MAP is less sensitive to environmental mismatch, but it suffers from low spatial resolution and a low peak-to-sidelobe ratio of ambiguity surface. These source localization metrics are herein improved with coherent approaches. Specifically, the coherent normalized MFP is extended to coherent matched autoproduct processing (CMAP), a difference frequency coherent algorithm that exploits correlations among the autoproducts at various difference frequencies and eliminates the phase factor of the source spectrum for passive source localization. Phase-only coherent matched autoproduct processing is a CMAP derivation technique that only uses phase information. Through simulations in a Munk sound-speed profile environment, sensitivity analysis in the South China Sea environment, and high signal-to-noise ratio experimental measurements, these two algorithms are validated as compared to the conventional MFP and incoherent MAP. Simulation investigations demonstrate that difference frequency coherent algorithms can suppress sidelobes while simultaneously enhancing the localization resolution and robustness. The experimental results generally support the findings of the simulations.
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Although large amount of effort has been invested in combating thermal quenching that severely degrades the performance of luminescent materials particularly at high temperatures, not much affirmative progress has been realized. Herein, we demonstrate that the Frenkel defect formed via controlled annealing of Sc2 (WO4 )3 :Ln (Ln=Yb, Er, Eu, Tb, Sm), can work as energy reservoir and back-transfer the stored excitation energy to Ln3+ upon heating. Therefore, except routine anti-thermal quenching, thermally enhanced 415-fold downshifting and 405-fold upconversion luminescence are even obtained in Sc2 (WO4 )3 :Yb/Er, which has set a record of both the Yb3+ -Er3+ energy transfer efficiency (>85 %) and the working temperature at 500 and 1073â K, respectively. Moreover, this design strategy is extendable to other hosts possessing Frenkel defect, and modulation of which directly determines whether enhanced or decreased luminescence can be obtained. This discovery has paved new avenues to reliable generation of high-temperature luminescence.
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KEY MESSAGE: Our results show that SPL12 plays a crucial role in regulating nodule development in Medicago sativa L. (alfalfa), and that AGL6 is targeted and downregulated by SPL12. Root architecture in plants is critical because of its role in controlling nutrient cycling, water use efficiency and response to biotic and abiotic stress factors. The small RNA, microRNA156 (miR156), is highly conserved in plants, where it functions by silencing a group of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors. We previously showed that transgenic Medicago sativa (alfalfa) plants overexpressing miR156 display increased nodulation, improved nitrogen fixation and enhanced root regenerative capacity during vegetative propagation. In alfalfa, transcripts of eleven SPLs, including SPL12, are targeted for cleavage by miR156. In this study, we characterized the role of SPL12 in root architecture and nodulation by investigating the transcriptomic and phenotypic changes associated with altered transcript levels of SPL12, and by determining SPL12 regulatory targets using SPL12-silencing and -overexpressing alfalfa plants. Phenotypic analyses showed that silencing of SPL12 in alfalfa caused an increase in root regeneration, nodulation, and nitrogen fixation. In addition, AGL6 which encodes AGAMOUS-like MADS box transcription factor, was identified as being directly targeted for silencing by SPL12, based on Next Generation Sequencing-mediated transcriptome analysis and chromatin immunoprecipitation assays. Taken together, our results suggest that SPL12 and AGL6 form a genetic module that regulates root development and nodulation in alfalfa.
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Medicago sativa , MicroARNs , Medicago sativa/fisiología , Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , Transcriptoma , Perfilación de la Expresión GénicaRESUMEN
A 56-day feeding trial was conducted to examine the preventive and reparative functions of host-associated probiotics against high soybean meal (SM)-induced negative effects in Japanese seabass (Lateolabrax japonicus). Fish continuously fed low SM (containing 16% SM) and high SM (containing 40% SM) diets were named as positive (PC) and negative (C) control, respectively. Preventive functions of probiotics were evaluated by continuously feeding diets LF3 (Lactococcus petauri LF3 supplemented in high SM diet, group PLF3) and LF4 (Bacillus siamensis LF4 supplemented in high SM diet, group PLF4), while reparative functions were estimated by feeding the high SM diet during 0-28 days, then feeding diets LF3 (group RLF3) and LF4 (group RLF4) until day 56. Compared with the group PC, suppressed growth and immunity, and damaged intestinal health were observed in the group C on days 28 and 56. Fish in groups PLF3 and PLF4, rather than in groups RLF3 and RLF4, showed higher growth compared with the group C and displayed similar immune status to the group PC, indicating that the initial and continued application of probiotic LF3 and LF4 can efficiently improve high SM induced growth and immune deficiency in Japanese seabass, but probiotics had limited reparative benefits when they were administrated at the middle of the feeding trial (28 d). Furthermore, probiotics showed good preventive functions and limited reparative functions on gut health via improving intestinal morphology and inflammation markers, for example, decreasing diamine oxidase activity and d-lactate content, while up-regulating anti-inflammatory TGF-ß1 expression and down-regulating pro-inflammatory TNF-α, IL-1ß, and IL-8 expressions. Moreover, dietary supplementation of probiotics (especially on day 56) could effectively shape the gut microbiota, such as significantly decreasing abundances of opportunistic pathogens (phylum Actinobacteria, genera Pseudomonas and Moheibacter on day 28, phylum Proteobacteria, genus Plesiomonas on day 56), significantly increasing gut microbial diversity and abundances of possible beneficial bacteria (phylum Bacteroidetes and genus Lactobacillus on day 28, phyla Firmicutes, Bacteroidetes and Cyanobacteria, genera Bacillus, Lactobacillus and Bacteroides on day 56). In conclusion, we evidenced for the first time that host-associated L. petauri LF3 and B. siamensis LF4 can provide effectively preventive and certain reparative functions against high SM-induced adverse effects in L. japonicus.
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Amina Oxidasa (conteniendo Cobre) , Probióticos , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Interleucina-8 , Lactatos , Lactobacillus , Probióticos/farmacología , Glycine max , Factor de Crecimiento Transformador beta1 , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro. METHODS: In this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins. RESULTS: We observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro. CONCLUSION: Our vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.
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Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Animales , Células de la Médula Ósea , Diferenciación Celular , Células Cultivadas , Glucocorticoides/toxicidad , Osteogénesis , RatasRESUMEN
BACKGROUND: Microorganisms, including Bacillus species are used to help control plant pathogens, thereby reducing reliance on synthetic pesticides in agriculture. Bacillus velezensis strain 1B-23 has been shown to reduce symptoms of bacterial disease caused by Clavibacter michiganensis subsp. michiganensis in greenhouse-grown tomatoes, with in vitro studies implicating the lipopeptide surfactin as a key antimicrobial. While surfactin is known to be effective against many bacterial pathogens, it is inhibitory to a smaller proportion of fungi which nonetheless cause the majority of crop diseases. In addition, knowledge of optimal conditions for surfactin production in B. velezensis is lacking. RESULTS: Here, B. velezensis 1B-23 was shown to inhibit in vitro growth of 10 fungal strains including Candida albicans, Cochliobolus carbonum, Cryptococcus neoformans, Cylindrocarpon destructans Fusarium oxysporum, Fusarium solani, Monilinia fructicola, and Rhizoctonia solani, as well as two strains of C. michiganensis michiganensis. Three of the fungal strains (C. carbonum, C. neoformans, and M. fructicola) and the bacterial strains were also inhibited by purified surfactin (surfactin C, or [Leu7] surfactin C15) from B. velezensis 1B-23. Optimal surfactin production occurred in vitro at a relatively low temperature (16 °C) and a slightly acidic pH of 6.0. In addition to surfactin, B. velenzensis also produced macrolactins, cyclic dipeptides and minor amounts of iturins which could be responsible for the bioactivity against fungal strains which were not inhibited by purified surfactin C. CONCLUSIONS: Our study indicates that B. velezensis 1B-23 has potential as a biocontrol agent against both bacterial and fungal pathogens, and may be particularly useful in slightly acidic soils of cooler climates.
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Bacillus/metabolismo , Agentes de Control Biológico/farmacología , Hongos/efectos de los fármacos , Lipopéptidos/farmacología , Péptidos Cíclicos/farmacología , Enfermedades de las Plantas/microbiología , Solanum lycopersicum/microbiología , Bacillus/química , Agentes de Control Biológico/metabolismo , Canadá , Hongos/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Lipopéptidos/metabolismo , Péptidos Cíclicos/metabolismo , Enfermedades de las Plantas/prevención & control , TemperaturaRESUMEN
A laser interferometer will be used in the spaceborne gravitational-wave detection missions to measure the inter-satellite optical pathlength variations. The phase readout system of the interferometer needs to be carefully designed and tested to accomplish a shot-noise-limited detection performance under the situation of pico-Watt level received lights. In this work, a scheme based on dual-tone acousto-optic diffraction is presented to verify the performance of the weak-light phase readout system. By optimizing the parameters of the photoreceiver and the local strong-light power, the signal-to-noise ratio of the beat-note signal is enhanced. Thanks to the scheme's common-mode noise rejections for the laser frequency noise, and the optical-path noise, etc., the differential phase noise has achieved a performance of 2×10-4 rad/Hz1/2, which is dominated by the weak-light (â¼13 pW) shot noise above the frequencies of 2 mHz.
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The 2,2-dimethyl-2H-chromene motif is widely found in many bioactive molecules, and is a privileged structure in the pharmaceutical arena. We have developed a concise and regioselective approach to chromenes and chromanes through an aryne-based synthetic strategy. A practical, gram-scale synthetic route to a chromene-type aryne precursor was explored. Subsequently, cyclization under mild conditions afforded tetracyclic xanthone skeletons with excellent regioselectivity. Our approach provides a concise strategy for the gram-scale synthesis of chromene-type xanthones such as 6-deoxyisojacareubin, cylindroxanthone D, staudtiixanthone D, brasilixanthone A and cudracuspixanthone O.
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The gram-scale synthesis of 5,6-, 6,7-, and 7,8-chromene/chromane-type aryne precursors and their applications in regioselective transformation to other functional derivatives is reported. Chromene/chromane-type arynes are generated under mild conditions, which can further undergo [2 + 2], [3 + 2], and [4 + 2] cycloaddition reactions, nucleophilic addition reactions, and σ-insertion reactions to produce structurally novel substituted chromenes and chromanes. The excellent regioselectivity of the reaction is facilitated by the oxygen-containing guiding groups at the ortho-position of the triple bond, which can be removed or switched to other functional groups including alkenyl, aryl, heteroaryl, and arylamino groups.
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Benzopiranos , Reacción de Cicloadición , Estructura MolecularRESUMEN
SPT6 is a conserved elongation factor that is associated with phosphorylated RNA polymerase II (RNAPII) during transcription. Recent transcriptome analysis in yeast mutants revealed its potential role in the control of transcription initiation at genic promoters. However, the mechanism by which this is achieved and how this is linked to elongation remains to be elucidated. Here, we present the genome-wide occupancy of Arabidopsis SPT6-like (SPT6L) and demonstrate its conserved role in facilitating RNAPII occupancy across transcribed genes. We also further demonstrate that SPT6L enrichment is unexpectedly shifted, from gene body to transcription start site (TSS), when its association with RNAPII is disrupted. Protein domains, required for proper function and enrichment of SPT6L on chromatin, are subsequently identified. Finally, our results suggest that recruitment of SPT6L at TSS is indispensable for its spreading along the gene body during transcription. These findings provide new insights into the mechanisms underlying SPT6L recruitment in transcription and shed light on the coordination between transcription initiation and elongation.
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Proteínas de Arabidopsis/fisiología , ARN Polimerasa II/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Secuenciación de Inmunoprecipitación de Cromatina , ADN de Plantas/genética , ADN de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes Sintéticos , Dominios Proteicos , Mapeo de Interacción de Proteínas , ARN Mensajero/biosíntesis , ARN de Planta/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Fracciones Subcelulares , Elongación de la Transcripción Genética , Sitio de Iniciación de la TranscripciónRESUMEN
Objective To investigate the expression and correlation of Runt-related transcription factor 3(RUNX3)and enhancer of zeste homolog 2(EZH2)in rectal cancer,and to reveal the relationship between the expression of RUNX3 and EZH2 and the sensitivity of XELOX regimen to neoadjuvant chemotherapy in locally advanced rectal cancer patients. Methods The carcinoma and paracancerous tissues of 31 patients with rectal adenocarcinoma and no preoperative antitumor therapy were selected as cancer group and paracancer group,respectively.The relative mRNA levels of RUNX3 and EZH2 in the two groups were measured by real-time quantitative reverse transcription-polymerase chain reaction,and the protein levels were determined by immunohistochemical assay.The expression of RUNX3 and EZH2 was compared between cancer tissue and paracancerous tissue.The pre-treatment wax blocks of 26 patients with locally advanced rectal cancer who received 3 cycles of XELOX regimen as neoadjuvant chemotherapy before surgery were selected as the pre-neoadjuvant therapy group,and the postoperative pathological wax blocks were selected as the post-neoadjuvant treatment group.Tumor regression grade(TRG)was determined to evaluate the efficacy of neoadjuvant therapy.Immunohistochemical assay was used to detect the protein levels of RUNX3 and EZH2 in the two groups,and then the relationship between the expression patterns of the two proteins and the efficacy of neoadjuvant chemotherapy was analyzed. Results Compared with paracancerous tissue,the cancer tissue showed down-regulated mRNA level and reduced positive protein expression rate of RUNX3,while up-regulated mRNA level(P=0.001)and increased positive protein expression rate of EZH2(P=0.022).The mRNA levels of RUNX3 and EZH2 in the cancer group were negatively correlated(r=-0.599,P=0.000).Twelve patients who received neoadjuvant chemotherapy reached TRG0-TRG2,and the overall effective rate of neoadjuvant chemotherapy was 46.15%(12/26).Compared with pre-neoadjuvant therapy group,the post-neoadjuvant therapy group had increased positive expression rate of RUNX3 protein(P=0.163)and decreased positive expression rate of EZH2 protein(P=0.095).In the pre-neoadjuvant therapy group,the effective rate of neoadjuvant chemotherapy was 75.00%(9/12)in patients with positive RUNX3 expression,77.78%(7/9)in patients with negative EZH2 expression,and 100%(7/7)in patients with positive expression of RUNX3 and negative expression of EZH2.Multivariate Logistic regression showed that the expression of RUNX3 protein was the factor influencing the efficacy of neoadjuvant chemotherapy. Conclusions The positive expression rate of RUNX3 in cancer tissue was lower than that in paracancerous tissue,while that of EZH2 showed the opposite trend.Neoadjuvant chemotherapy may affect the expression of RUNX3 and EZH2 in rectal cancer.The patients with high RUNX3 expression and low EZH2 expression in locally advanced rectal cancer were more sensitive to neoadjuvant chemotherapy with XELOX regimen.