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Titanium alloys are advanced lightweight materials, indispensable for many critical applications1,2. The mainstay of the titanium industry is the α-ß titanium alloys, which are formulated through alloying additions that stabilize the α and ß phases3-5. Our work focuses on harnessing two of the most powerful stabilizing elements and strengtheners for α-ß titanium alloys, oxygen and iron1-5, which are readily abundant. However, the embrittling effect of oxygen6,7, described colloquially as 'the kryptonite to titanium'8, and the microsegregation of iron9 have hindered their combination for the development of strong and ductile α-ß titanium-oxygen-iron alloys. Here we integrate alloy design with additive manufacturing (AM) process design to demonstrate a series of titanium-oxygen-iron compositions that exhibit outstanding tensile properties. We explain the atomic-scale origins of these properties using various characterization techniques. The abundance of oxygen and iron and the process simplicity for net-shape or near-net-shape manufacturing by AM make these α-ß titanium-oxygen-iron alloys attractive for a diverse range of applications. Furthermore, they offer promise for industrial-scale use of off-grade sponge titanium or sponge titanium-oxygen-iron10,11, an industrial waste product at present. The economic and environmental potential to reduce the carbon footprint of the energy-intensive sponge titanium production12 is substantial.
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Anthocyanin generation in apples (Malus domestica) and the pigmentation that results from it may be caused by irradiation and through administration of methyl jasmonate (MeJA). However, their regulatory interrelationships associated with fruit coloration are not well defined. To determine whether MdERF109, a transcription factor (TF) involved in light-mediated coloration and anthocyanin biosynthesis, has synergistic effects with other proteins, we performed a yeast two-hybrid assessment and identified another TF, MdWER. MdWER was induced by MeJA treatment, and although overexpression of MdWER alone did not promote anthocyanin accumulation co-overexpression with MdERF109 resulted in significantly increase in anthocyanin biosynthesis. MdWER may form a protein complex with MdERF109 to promote anthocyanin accumulation by enhancing combinations between the proteins and their corresponding genes. In addition, MdWER, as a MeJA responsive protein, interacts with the anthocyanin repressor MdJAZ2. Transient co-expression in apple fruit and protein interaction assays allowed us to conclude that MdERF109 and MdJAZ2 interact with MdWER and take part in the production of anthocyanins upon MeJA treatment and irradiation. Our findings validate a role for the MdERF109-MdWER-MdJAZ2 module in anthocyanin biosynthesis and uncover a novel mechanism for how light and MeJA signals are coordinated anthocyanin biosynthesis in apple fruit.
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Acetatos , Antocianinas , Ciclopentanos , Frutas , Regulação da Expressão Gênica de Plantas , Luz , Malus , Oxilipinas , Proteínas de Plantas , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Antocianinas/metabolismo , Antocianinas/biossíntese , Acetatos/farmacologia , Acetatos/metabolismo , Malus/metabolismo , Malus/genética , Malus/efeitos da radiação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Frutas/metabolismo , Frutas/genética , Frutas/efeitos da radiação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Reguladores de Crescimento de Plantas/metabolismoRESUMO
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.
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Carcinoma , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Neoplasias de Cabeça e Pescoço/genética , Células Epiteliais , Microambiente Tumoral/genéticaRESUMO
Fungal phytopathogens cause significant reductions in agricultural yields annually, and overusing chemical fungicides for their control leads to environmental pollution and the emergence of resistant pathogens. Exploring natural isolates with strong antagonistic effects against pathogens can improve our understanding of their ecology and develop new treatments for the future. We isolated and characterized a novel bacterial strain associated with the species Burkholderia cenocepacia, termed APO9, which strongly inhibits Zymoseptoria tritici, a commercially important pathogenic fungus causing Septoria tritici blotch in wheat. Additionally, this strain exhibits inhibitory activity against four other phytopathogens. We found that physical contact plays a crucial role for APO9's antagonistic capacity. Genome sequencing of APO9 and biosynthetic gene cluster (BGC) analysis identified nine classes of BGCs and three types of secretion systems (types II, III, and IV), which may be involved in the inhibition of Z. tritici and other pathogens. To identify genes driving APO9's inhibitory activity, we screened a library containing 1,602 transposon mutants and identified five genes whose inactivation reduced inhibition efficiency. One such gene encodes for a diaminopimelate decarboxylase located in a terpenoid biosynthesis gene cluster. Phylogenetic analysis revealed that while some of these genes are also found across the Burkholderia genus, as well as in other Betaproteobacteria, the combination of these genes is unique to the Burkholderia cepacia complex. These findings suggest that the inhibitory capacity of APO9 is complex and not limited to a single mechanism, and may play a role in the interaction between various Burkholderia species and various phytopathogens within diverse plant ecosystems. IMPORTANCE: The detrimental effects of fungal pathogens on crop yields are substantial. The overuse of chemical fungicides contributes not only to environmental pollution but also to the emergence of resistant pathogens. Investigating natural isolates with strong antagonistic effects against pathogens can improve our understanding of their ecology and develop new treatments for the future. We discovered and examined a unique bacterial strain that demonstrates significant inhibitory activity against several phytopathogens. Our research demonstrates that this strain has a wide spectrum of inhibitory actions against plant pathogens, functioning through a complex mechanism. This plays a vital role in the interactions between plant microbiota and phytopathogens.
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Ascomicetos , Burkholderia cenocepacia , Doenças das Plantas , Ascomicetos/genética , Burkholderia cenocepacia/genética , Burkholderia cenocepacia/efeitos dos fármacos , Doenças das Plantas/microbiologia , Triticum/microbiologia , Antibiose , Família MultigênicaRESUMO
BACKGROUND: Cardiovascular disease (CVD) is closely associated with the triglyceride glucose (TyG) index and its related indicators, particularly its combination with obesity indices. However, there is limited research on the relationship between changes in TyG-related indices and CVD, as most studies have focused on baseline TyG-related indices. METHODS: The data for this prospective cohort study were obtained from the China Health and Retirement Longitudinal Study. The exposures were changes in TyG-related indices and cumulative TyG-related indices from 2012 to 2015. The K-means algorithm was used to classify changes in each TyG-related index into four classes (Class 1 to Class 4). Multivariate logistic regressions were used to evaluate the associations between the changes in TyG-related indices and the incidence of CVD. RESULTS: In total, 3243 participants were included in this study, of whom 1761 (54.4%) were female, with a mean age of 57.62 years at baseline. Over a 5-year follow-up, 637 (19.6%) participants developed CVD. Fully adjusted logistic regression analyses revealed significant positive associations between changes in TyG-related indices, cumulative TyG-related indices and the incidence of CVD. Among these changes in TyG-related indices, changes in TyG-waist circumference (WC) showed the strongest association with incident CVD. Compared to the participants in Class 1 of changes in TyG-WC, the odds ratio (OR) for participants in Class 2 was 1.41 (95% confidence interval (CI) 1.08-1.84), the OR for participants in Class 3 was 1.54 (95% CI 1.15-2.07), and the OR for participants in Class 4 was 1.94 (95% CI 1.34-2.80). Moreover, cumulative TyG-WC exhibited the strongest association with incident CVD among cumulative TyG-related indices. Compared to the participants in Quartile 1 of cumulative TyG-WC, the OR for participants in Quartile 2 was 1.33 (95% CI 1.00-1.76), the OR for participants in Quartile 3 was 1.46 (95% CI 1.09-1.96), and the OR for participants in Quartile 4 was 1.79 (95% CI 1.30-2.47). CONCLUSIONS: Changes in TyG-related indices are independently associated with the risk of CVD. Changes in TyG-WC are expected to become more effective indicators for identifying individuals at a heightened risk of CVD.
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Biomarcadores , Glicemia , Doenças Cardiovasculares , Obesidade , Triglicerídeos , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/sangue , Estudos Prospectivos , Triglicerídeos/sangue , Incidência , Medição de Risco , China/epidemiologia , Glicemia/metabolismo , Obesidade/epidemiologia , Obesidade/diagnóstico , Obesidade/sangue , Idoso , Biomarcadores/sangue , Estudos Longitudinais , Fatores de Tempo , Prognóstico , Fatores de Risco de Doenças Cardíacas , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Anthocyanin pigments contribute to plant coloration and are valuable sources of antioxidants in the human diet as components of fruits and vegetables. Their production is known to be induced by light in apple fruit (Malus domestica); however, the underlying molecular mechanism responsible for early-stage light-induced anthocyanin biosynthesis remains unclear. Here, we identified an ethylene response factor (ERF) protein, ERF109, involved in light-induced anthocyanin biosynthesis and found that it promotes coloration by directly binding to anthocyanin-related gene promoters. Promoter::ß-glucuronidase reporter analysis and Hi-C sequencing showed that a long noncoding RNA, MdLNC499, located nearby MdERF109, induces the expression of MdERF109. A W-box cis-element in the MdLNC499 promoter was found to be regulated by a transcription factor, MdWRKY1. Transient expression in apple fruit and stable transformation of apple calli allowed us to reconstruct a MdWRKY1-MdLNC499-MdERF109 transcriptional cascade in which MdWRKY1 is activated by light to increase the transcription of MdLNC499, which in turn induces MdERF109. The MdERF109 protein induces the expression of anthocyanin-related genes and the accumulation of anthocyanins in the early stages of apple coloration. Our results provide a platform for better understanding the various regulatory mechanisms involved in light-induced apple fruit coloration.
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Antocianinas/metabolismo , Frutas/metabolismo , Malus/genética , Proteínas de Plantas/genética , RNA Longo não Codificante/genética , RNA de Plantas/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Frutas/crescimento & desenvolvimento , Malus/metabolismo , Proteínas de Plantas/metabolismo , RNA Longo não Codificante/metabolismo , RNA de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Inhibition of autophagy increases the sensitivity of tumor cells to radiotherapy and chemotherapy and improves the therapeutic effect on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy has been proven to further improve the efficiency of cancer treatment. As such, combining autophagy inhibition with PDT and chemotherapy may represent a potentially effective new strategy for cancer treatment. However, currently widely studied autophagy inhibitors inevitably produce various toxic side effects due to their inherent pharmacological activity. To overcome this constraint, in this study, we designed an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA + NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN), Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA (MUCE) groups were set up separately as controls. Based on a combination of autophagy inhibition and PDT, the average particle size of MUCEN was 197 nm, which can simultaneously achieve the double encapsulation of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed that MUCE was efficiently endocytosed by 4T1 cells under near-infrared light irradiation. Further, in vivo tests revealed that MUCE dramatically inhibited tumor growth. Immunohistochemistry results indicated that MUCE efficiently increased the expression of autophagy inhibitors p62 and LC3 in tumor tissues. The synergistic effect of autophagy inhibition and PDT with MUCE exhibited superior tumor suppression, providing an innovative approach to cancer treatment.
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OBJECTIVES: This study aimed to explore the endothelialization process and assess the potential association between endothelialization and peri-device leak (PDL) following Watchman implantation via a quantitative method. METHODS: This is a single-center retrospective study of consecutive patients undergoing LAAO between December 2015 and November 2021. Device endothelialization, compared between PDL and non-PDL group, were quantitatively analyzed based on hypoattenuated thickening in cardiac computed tomography angiography (CCTA). Advancement in endothelialization over time were explored using the Cochran-Armitage test and generalized estimating equation approach. Potential risk factors of delayed endothelialization were analyzed using the Cox proportional-hazards model. RESULTS: A total of 172 patients (mean age, 68 years ± 10 [standard deviation], 114 men) were finally included. The average endothelialization ratio of the study population was 89.8 ± 7.2 percent. In the follow-up period of postprocedural 3 months to more than 12 months, an incremental trend of endothelialization over time was observed with the ratio of 85.8 ± 8.0, 89.6 ± 7.6, 92.2 ± 4.5, 94.3 ± 2.9 percent, respectively (p < 0.0001). Notably, patients without PDL exhibited a swifter advancement in endothelialization compared to those with PDL, irrespective of device size. The multivariable Cox regression model showed that PDL (HR = 2.113, 95%CI: 1.300-3.435, p = 0.003), DSP (HR = 1.717, 95%CI: 1.113-2.647, p = 0.014) were independent risk factors of delayed endothelialization. CONCLUSION: CCTA holds promise as an effective means of quantitatively assessing device endothelialization. Endothelialization advanced gradually over time, with PDL potentially impeding device endothelialization. CLINICAL RELEVANCE STATEMENT: A comprehensive understanding of the correlation between endothelialization ratio, time, and residual shunt can establish a more dependable foundation for determining the appropriate anticoagulation treatment following left atrial appendage closure. KEY POINTS: Current recommendations for postleft atrial appendage occlusion anti-platelet and anticoagulation therapy are based on animal studies. Cardiac computed tomography angiography (CCTA) combined with the UNet neural network model enables the quantitative assessment of device endothelialization. This technique will allow for additional studies to better understand device endothelialization to optimize treatments in this population.
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Ocular dominance (OD), a commonly used concept in clinical practice, plays an important role in optometry and refractive surgery. With the development of refractive cataract surgery, the refractive function of the intraocular lens determines the achievement of the postoperative full range of vision based on the retinal defocus blur suppression and binocular monovision principle. Therefore, OD plays an important role in cataract surgery. OD is related to the visual formation of the cerebral cortex, and its plasticity suggests that visual experience can influence the visual system. Cataract surgery changes the visual experience and transforms the dominant eye, which confirms the plasticity of the visual system. Based on the concept and mechanism of OD, this review summarizes the application of OD in cataract surgery.
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Extração de Catarata , Catarata , Cristalino , Humanos , Acuidade Visual , Dominância Ocular , Catarata/complicaçõesRESUMO
Primary hypertension is a significant risk factor for cardiovascular diseases. However, the pathogenesis of primary hypertension involves multiple biological processes, including the nervous system, circulatory system, endocrine system, and more. Despite extensive research, there is no clear understanding of the regulatory mechanism underlying its pathogenesis. In recent years, miRNAs have gained attention as a regulatory factor capable of modulating the expression of related molecules through gene silencing. Therefore, exploring differentially expressed miRNAs in patients with essential hypertension (EH) may offer a novel approach for future diagnosis and treatment of EH. This study included a total of twenty Han Chinese population samples from Hefei, China. The samples consisted of 10 healthy individuals and 10 patients with EH. Statistical analysis was conducted to analyze the general information of the two-sample groups. High-throughput sequencing and base identification were performed to obtain the original sequencing sequences. These sequences were then annotated using various databases including Rfam, cDNA sequences, species repetitive sequences library, and miRBase database. The number of miRNA species contained in the samples was measured. Next, TPM values were calculated to determine the expression level of each miRNA. The bioinformatics of the differentiated miRNAs were analyzed using the OECloud tool, and RPM values were calculated. Furthermore, the reliability of the expression was analyzed by calculating the area under the Roc curve using the OECloud tools. Statistical analysis revealed no significant differences between the two samples in terms of age distribution, gender composition, smoking history, and alcohol consumption history (P > 0.05). However, there was a notable presence of family genetic history and high BMI in the EH population (P < 0.05). The sequencing results identified a total of 245 miRNAs, out of which 16 miRNAs exhibited differential expression. Among the highly expressed miRNAs were let-7d-5p, miR-101-3p, miR-122-5p, miR-122b-3p, miR-192-5p, and miR-6722-3p. On the other hand, the lowly expressed miRNAs included miR-103a-3p, miR-16-5p, miR-181a-2-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-221-3p, miR-30d-5p, miR-342-5p, and miR-543. This study initially identified 16 miRNAs that are aberrantly expressed and function in various processes associated with the onset and progression of essential hypertension. These miRNAs have the potential to be targeted for future diagnosis and treatment of EH. However, further samples are required to provide additional support for this study.
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Cardiovascular diseases pose a long-term risk to human health. This study focuses on the rich-spectrum mechanical vibrations generated during cardiac activity. By combining Fourier series theory, we propose a multi-frequency vibration model for the heart, decomposing cardiac vibration into frequency bands and establishing a systematic interpretation for detecting multi-frequency cardiac vibrations. Based on this, we develop a small multi-frequency vibration sensor module based on flexible polyvinylidene fluoride (PVDF) films, which is capable of synchronously collecting ultra-low-frequency seismocardiography (ULF-SCG), seismocardiography (SCG), and phonocardiography (PCG) signals with high sensitivity. Comparative experiments validate the sensor's performance and we further develop an algorithm framework for feature extraction based on 1D-CNN models, achieving continuous recognition of multiple vibration features. Testing shows that the recognition coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) of the 8 features are 0.95, 2.18 ms, and 4.89 ms, respectively, with an average prediction speed of 60.18 us/point, meeting the re-quirements for online monitoring while ensuring accuracy in extracting multiple feature points. Finally, integrating the vibration model, sensor, and feature extraction algorithm, we propose a dynamic monitoring system for multi-frequency cardiac vibration, which can be applied to portable monitoring devices for daily dynamic cardiac monitoring, providing a new approach for the early diagnosis and prevention of cardiovascular diseases.
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Doenças Cardiovasculares , Vibração , Humanos , Coração , Algoritmos , FonocardiografiaRESUMO
Excessive use of tetracycline antibiotics in poultry farming results in significant concentrations of these drugs and tetracycline resistance genes (TRGs) in chicken manure, impacting both environmental and human health. Our research represents the first investigation into the removal dynamics of chlortetracycline (CTC) and TRGs in different layers of an ex situ fermentation system (EFS) for chicken waste treatment. By pinpointing and analyzing dominant TRGs-harboring bacteria and their interactions with environmental variables, we've closed an existing knowledge gap. Findings revealed that CTC's degradation half-lives spanned 3.3-5.8 days across different EFS layers, and TRG removal efficiency ranged between 86.82% and 99.52%. Network analysis highlighted Proteobacteria and Actinobacteria's essential roles in TRGs elimination, whereas Chloroflexi broadened the potential TRG hosts in the lower layer. Physical and chemical conditions within the EFS influenced microbial community diversity, subsequently impacting TRGs and integrons. Importantly, our study reports that the middle EFS layer exhibited superior performance in eliminating CTC and key TRGs (tetW, tetG, and tetX) as well as intI2. Our work transcends immediate health and environmental remediation by offering insights that encourage sustainable agriculture practices.
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Clortetraciclina , Esterco , Animais , Humanos , Esterco/análise , Galinhas , Fermentação , Antibacterianos/farmacologia , Antibacterianos/análise , Tetraciclina , Genes BacterianosRESUMO
Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 - 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 - 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 - 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 - 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 - 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 - 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 - 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 - 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 - 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95%CI: -109.04 - -56.90; P<0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.
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Perda Sanguínea Cirúrgica , Dexmedetomidina , Hemodinâmica , Coluna Vertebral , Dexmedetomidina/administração & dosagem , Humanos , Hemodinâmica/efeitos dos fármacos , Coluna Vertebral/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Hipotensão/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4-hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.
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The construction of multiple continuous fully substituted carbon centers, which serve as unique structural motif in natural products, is a challenging topic in organic synthesis. Herein, we report a hydrated [3+2] cyclotelomerization of butafulvenes to create contiguous fully substituted carbon backbone. In the presence of scandium triflate, all-carbon skeleton with spiro fused tricyclic ring can be constructed in high diastereoselectivity by utilizing butafulvene as the synthon. Mechanistic studies suggest that this atom-economic reaction probably proceeds through a synergistic process containing butafulvenes dimerization and nucleophilic attack by water. In addition, the tricyclic product can undergo a series of synthetic derivatizations, which highlights the potential applications of this strategy. The recyclability of Sc(OTf)3 has also been demonstrated to show its robust performance in this hydrated cyclotelomerization.
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Light is known to regulate anthocyanin pigment biosynthesis in plants on several levels, but the significance of protein phosphorylation in light-induced anthocyanin accumulation needs further investigation. In this study, we investigated the dynamics of the apple fruit phosphoproteome in response to light, using high-performance liquid chromatography-tandem mass spectrometry analysis. Among the differentially phosphorylated proteins, the bZIP (basic leucine zipper) transcription factor, HY5, which has been identified as an anthocyanin regulator, was rapidly activated by light treatment of the fruit. We hypothesized that phosphorylated MdHY5 may play a role in light-induced anthocyanin accumulation of apple fruit. Protein interaction and phosphorylation assays showed that mitogen-activated protein kinase MdMPK6 directly interacted with, and activated, MdHY5 via phosphorylation under light conditions, thereby increasing its stability. Consistent with this finding, the suppression of the mitogen-activated protein kinase genes MdMPK6 or MdHY5 resulted in an inhibition of anthocyanin accumulation, and further showed that light-induced anthocyanin accumulation is dependent on MdMPK6 kinase activity, and is required for maximum MdHY5 activity. Under light conditions, active MdMPK6 phosphorylated MdHY5 leading to accumulation of phospho-MdHY5, which enhanced the binding of MdHY5 to its target anthocyanin related genes in fruit. Our findings reveal an MdMPK6-MdHY5 phosphorylation pathway in light-induced anthocyanin accumulation, providing new insights into the regulation of light-induced anthocyanin biosynthesis in apple fruit at both the transcriptional and post-translational levels.
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Malus , Malus/genética , Malus/metabolismo , Frutas/genética , Frutas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Antocianinas , Fosforilação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Anthocyanin production in apple (Malus domestica) fruit and their consequent coloration can be induced by high-light treatment. The hormone ethylene is also essential for this coloration, but the regulatory relationships that link ethylene and light with anthocyanin-associated coloration are not well defined. In this study, we observed that high-light treatment of apple fruit increased anthocyanin accumulation more than moderate-light treatment did and was the main contributor of induced ethylene production and activation of anthocyanin biosynthesis. A transcriptome study of light-treated apple fruit suggested that a long noncoding RNA (lncRNA), MdLNC610, the corresponding gene of which is physically located downstream from the 1-aminocyclopropane-1-carboxylate oxygenase (ACO) ethylene biosynthesis gene MdACO1, likely affects anthocyanin biosynthesis under high-light treatment. Expression and promoter ß-glucuronidase reporter analyses further showed that MdLNC610 upregulates expression of MdACO1 and so likely participates in high-light-induced ethylene biosynthesis. Overexpression of MdACO1 and MdLNC610 in apple fruit and calli indicated that a major increase in MdLNC610 expression activates MdACO1 expression, thereby causing an increase in ethylene production and anthocyanin levels. These results suggest that MdLNC610 participates in the regulation of high-light-induced anthocyanin production by functioning as a positive regulator to promote MdACO1 expression and ethylene biosynthesis. Our study provides insights into the relationship between mRNA and lncRNA networks in the ethylene biosynthetic pathway and anthocyanin accumulation in apple fruit.
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Malus , RNA Longo não Codificante , Antocianinas/metabolismo , Etilenos/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
In allusion to the privacy and security problems in 3D point cloud classification, a novel privacy protection method for 3D point cloud classification based on optical chaotic encryption scheme is proposed and implemented in this paper for the first time. The mutually coupled spin-polarized vertical-cavity surface-emitting lasers (MC-SPVCSELs) subject to double optical feedback (DOF) are studied to generate optical chaos for permutation and diffusion encryption process of 3D point cloud. The nonlinear dynamics and complexity results demonstrate that the MC-SPVCSELs with DOF have high chaotic complexity and can provide tremendously large key space. All the test-sets of ModelNet40 dataset containing 40 object categories are encrypted and decrypted by the proposed scheme, and then the classification results of 40 object categories for original, encrypted, and decrypted 3D point cloud are entirely enumerated through the PointNet++. Intriguingly, the class accuracies of the encrypted point cloud are nearly all equal to 0.0000% except for the plant class with 100.0000%, indicating the encrypted point cloud cannot be classified and identified. The decryption class accuracies are very close to the original class accuracies. Therefore, the classification results verify that the proposed privacy protection scheme is practically feasible and remarkably effective. Additionally, the encryption and decryption results show that the encrypted point cloud images are ambiguous and unrecognizable, while the decrypted point cloud images are identical to original images. Moreover, this paper improves the security analysis via analyzing 3D point cloud geometric features. Eventually, various security analysis results validate that the proposed privacy protection scheme has high security level and good privacy protection effect for 3D point cloud classification.
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Quantum entanglement is an indispensable resource for implementing quantum information processing. The scale of quantum entanglement directly determines its quantum information processing capability. Therefore, it is of great importance to generate ultra-large-scale (ULS) quantum entanglement for the development of quantum information science and technology. Many efforts have been made to increase the scale of quantum entanglement. Recently, time-domain multiplexing has been introduced into continuous-variable (CV) quantum systems to greatly enlarge the scale of quantum entanglement. In this Letter, based on a time-delayed quantum interferometer, we theoretically propose and experimentally demonstrate a scheme for generating an ULS CV deterministic entanglement containing 2×20 400 optical modes. In addition, such ULS entanglement contains 81 596 squeezed modes. Our results provide a new platform for implementing ULS CV quantum information processing.
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BACKGROUNDS: Study concerning the clinical features, electrocardiogram (ECG) findings and outcomes in patients presenting with acute total occlusion of left main coronary artery (LM) without collateral circulation is limited. METHODS: 25 patients with acute total LM occlusion without collateral circulation by emergency coronary angiography, from muti-center registry, were retrospectively studied. The clinical and angiographic characteristics, ECG and in-hospital mortality were reviewed. RESULTS: Nineteen patients (76%) presented with cardiogenic shock. Twelve (60%, 12/20) patients had coronary slow flow or no reflow phenomenon after primary percutaneous coronary intervention (PCI). The in-hospital mortality rate was 88% (n = 22). All the patients presented with ST-segment elevation myocardial ischemia (STEMI) pattern, mostly involving leads I, aVL, V2, V3, V4, V5 and ST-segment depression in leads II, III and aVF. CONCLUSIONS: Acute total LM occlusion without collateral circulation portends high in-hospital mortality. Anterior ST elevation in the precordial leads from V2 to V4 through V6, and ST elevation in leads I and aVL, accompanying with ST depression in the inferior leads is associated with acute total LM occlusion without collateral circulation.