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1.
JMIR Form Res ; 8: e43119, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052994

RESUMEN

BACKGROUND: Throughout the COVID-19 pandemic, multiple policies and guidelines were issued and updated for health care personnel (HCP) for COVID-19 testing and returning to work after reporting symptoms, exposures, or infection. The high frequency of changes and complexity of the policies made it difficult for HCP to understand when they needed testing and were eligible to return to work (RTW), which increased calls to Occupational Health Services (OHS), creating a need for other tools to guide HCP. Chatbots have been used as novel tools to facilitate immediate responses to patients' and employees' queries about COVID-19, assess symptoms, and guide individuals to appropriate care resources. OBJECTIVE: This study aims to describe the development of an RTW chatbot and report its impact on demand for OHS support services during the first Omicron variant surge. METHODS: This study was conducted at Mass General Brigham, an integrated health care system with over 80,000 employees. The RTW chatbot was developed using an agile design methodology. We mapped the RTW policy into a unified flow diagram that included all required questions and recommendations, then built and tested the chatbot using the Microsoft Azure Healthbot Framework. Using chatbot data and OHS call data from December 10, 2021, to February 17, 2022, we compared OHS resource use before and after the deployment of the RTW chatbot, including the number of calls to the OHS hotline, wait times, call length, and time OHS hotline staff spent on the phone. We also assessed Centers for Disease Control and Prevention data for COVID-19 case trends during the study period. RESULTS: In the 5 weeks post deployment, 5575 users used the RTW chatbot with a mean interaction time of 1 minute and 17 seconds. The highest engagement was on January 25, 2022, with 368 users, which was 2 weeks after the peak of the first Omicron surge in Massachusetts. Among users who completed all the chatbot questions, 461 (71.6%) met the RTW criteria. During the 10 weeks, the median (IQR) number of daily calls that OHS received before and after deployment of the chatbot were 633 (251-934) and 115 (62-167), respectively (U=163; P<.001). The median time from dialing the OHS phone number to hanging up decreased from 28 minutes and 22 seconds (IQR 25:14-31:05) to 6 minutes and 25 seconds (IQR 5:32-7:08) after chatbot deployment (U=169; P<.001). Over the 10 weeks, the median time OHS hotline staff spent on the phone declined from 3 hours and 11 minutes (IQR 2:32-4:15) per day to 47 (IQR 42-54) minutes (U=193; P<.001), saving approximately 16.8 hours per OHS staff member per week. CONCLUSIONS: Using the agile methodology, a chatbot can be rapidly designed and deployed for employees to efficiently receive guidance regarding RTW that complies with the complex and shifting RTW policies, which may reduce use of OHS resources.

2.
Hortic Res ; 11(7): uhae155, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39005999

RESUMEN

Stable genetic transformation of peach [Prunus persica (L.) Batsch] still faces many technical challenges, and existing transient expression methods are limited by tissue type or developmental stage, making it difficult to conduct functional analysis of genes regulating shoot growth. To overcome this dilemma, we developed a three-step method for efficient analysis of gene functions during peach seedling growth and development. This method resulted in transformation frequencies ranging from 48 to 87%, depending on the gene. From transformation of germinating seeds to phenotyping of young saplings took just 1.5 months and can be carried out any time of year. To test the applicability of this method, the function of three tree architecture-related genes, namely PpPDS, PpMAX4, and PpWEEP, and two lateral root-related genes, PpIAA14-1 and -2, were confirmed. Since functional redundancy can challenge gene functional analyses, tests were undertaken with the growth-repressor DELLA, which has three homologous genes, PpDGYLA (DG), PpDELLA1 (D1), and -2 (D2), in peach that are functionally redundant. Silencing using a triple-target vector (TRV2-DG-D1-D2) resulted in transgenic plants taller than those carrying just TRV2-DG or TRV2. Simultaneously silencing the three DELLA genes also attenuated the stature of two dwarf genotypes, 'FHSXT' and 'HSX', which normally accumulate DELLA proteins. Our study provides a method for the functional analysis of genes in peach and can be used for the study of root, stem, and leaf development. We believe this method can be replicated in other woody plants.

3.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000180

RESUMEN

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 µg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.


Asunto(s)
Péptidos Antimicrobianos , Pruebas de Sensibilidad Microbiana , Animales , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Bacterias Gramnegativas/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/genética , Humanos
4.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38984889

RESUMEN

Counter-gravity casting (CGC) aims to eliminate turbulent melt flow and defect formation during filling and subsequent solidification by pushing high-temperature melt into the mold cavity against gravity with regulated pressure. However, limited by the opaqueness of molten metals and the complexity of the CGC apparatus, it is extremely difficult to directly quantify the high-velocity mold filling and pressurized solidification in real-time. Here, we report the design and characterization of a CGC system capable of in situ monitoring of mold filling and subsequent solidification processes in the synchrotron beamlines by deploying a high-energy, high-speed synchrotron x-ray imaging technique. The high-velocity melt flow and dendrite growth during pressurized solidification have been quantified for systematical process parameter analysis by investigating time-resolved x-ray images of an exemplary Al-Cu alloy. The high-speed imaging results demonstrate that the in situ CGC system provides a useful way to better understand the fundamentals of mold filling, pressurized solidification, and experimental inputs for high-fidelity modeling in scientific and industrial applications.

5.
Front Plant Sci ; 15: 1427972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919824

RESUMEN

To determine the appropriate seeding rate for machine-transplanted hybrid rice, field experiments were conducted during 2022-2023 using the hybrid rice variety Huazhe You 210 as the material. Four seeding rate treatments were set up: 40 (T1), 60 (T2), 80 (T3) and 100 g tray-1 (T4), to investigate the effects of seeding rate on the seedling quality, transplanting quality, yield formation, and economic benefits of high-quality indica hybrid rice seedlings. The results showed that with increasing seeding rate, the seedling base stem diameter and seedling plumpness of hybrid rice seedlings decreased, but the root entwining force gradually increased, leading to a deterioration in individual seedling quality but an improvement in collective characteristics. As the seeding rate increased, the missing hill rate during mechanical planting of hybrid rice significantly decreased, while the number of seedlings per hill and the damaged seedling rate showed an upward trend. The growth volume of tillers, tillering spikelet rate, and harvest index of hybrid rice in the field showed an overall downward trend with increasing seeding rate, while the accumulation of dry matter initially increased and then decreased. The yield and economic benefits of hybrid rice grains showed an initial increase followed by a decrease with increasing seeding rate, with the highest yield and economic benefits achieved with the T2 treatment. In conclusion, the appropriate seeding rate for machine-transplanted hybrid rice is T2 (60 g tray-1), which can maintain good seedling quality and improve transplanting quality, coordinate larger collective growth and appropriate harvest index, contributing to high yield and good economic benefits.

6.
J Am Coll Radiol ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866067

RESUMEN

Medical extended reality (MXR), encompassing augmented reality, virtual reality, and mixed reality (MR), presents a novel paradigm in radiology training by offering immersive, interactive, and realistic learning experiences in health care. Although traditional educational tools in the field of radiology are essential, it is necessary to capitalize on the innovative and emerging educational applications of extended reality (XR) technologies. At the most basic level of learning anatomy, XR has been extensively used with an emphasis on its superiority over conventional learning methods, especially in spatial understanding and recall. For imaging interpretation, XR has fostered the concepts of virtual reading rooms by enabling collaborative learning environments and enhancing image analysis and understanding. Moreover, image-guided interventions in interventional radiology have witnessed an uptick in XR utilization, illustrating its effectiveness in procedural training and skill acquisition for medical students and residents in a safe and risk-free environment. However, there remain several challenges and limitations for XR in radiology education, including technological, economic, and ergonomic challenges and and integration into existing curricula. This review explores the transformative potential of MXR in radiology education and training along with insights on the future of XR in radiology education, forecasting advancements in immersive simulations, artificial intelligence integration for personalized learning, and the potential of cloud-based XR platforms for remote and collaborative training. In summation, MXR's burgeoning role in reshaping radiology education offers a safer, scalable, and more efficient training model that aligns with the dynamic healthcare landscape.

7.
New Phytol ; 243(3): 1050-1064, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38872462

RESUMEN

Branch number is one of the most important agronomic traits of fruit trees such as peach. Little is known about how LncRNA and/or miRNA modules regulate branching through transcription factors. Here, we used molecular and genetic tools to clarify the molecular mechanisms underlying brassinosteroid (BR) altering plant branching. We found that the number of sylleptic branch and BR content in pillar peach ('Zhaoshouhong') was lower than those of standard type ('Okubo'), and exogenous BR application could significantly promote branching. PpTCP4 expressed great differentially comparing 'Zhaoshouhong' with 'Okubo'. PpTCP4 could directly bind to DWARF2 (PpD2) and inhibited its expression. PpD2 was the only one differentially expressed key gene in the path of BR biosynthesis. At the same time, PpTCP4 was identified as a target of miR6288b-3p. LncRNA1 could act as the endogenous target mimic of miR6288b-3p and repress expression of miR6288b-3p. Three deletions and five SNP sites of lncRNA1 promoter were found in 'Zhaoshouhong', which was an important cause of different mRNA level of PpTCP4 and BR content. Moreover, overexpressed PpTCP4 significantly inhibited branching. A novel mechanism in which the lncRNA1-miR6288b-3p-PpTCP4-PpD2 module regulates peach branching number was proposed.


Asunto(s)
Brasinoesteroides , Regulación de la Expresión Génica de las Plantas , MicroARNs , Proteínas de Plantas , Prunus persica , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Prunus persica/genética , Prunus persica/crecimiento & desarrollo , Prunus persica/metabolismo , Brasinoesteroides/metabolismo , Brasinoesteroides/biosíntesis , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas/genética , Secuencia de Bases , Polimorfismo de Nucleótido Simple/genética , Genes de Plantas
8.
Exp Brain Res ; 242(7): 1645-1658, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38789796

RESUMEN

Traumatic brain injury (TBI) mechanism and severity are heterogenous clinically, resulting in a multitude of physical, cognitive, and behavioral deficits. Impact variability influences the origin, spread, and classification of molecular dysfunction which limits strategies for comprehensive clinical intervention. Indeed, there are currently no clinically approved therapeutics for treating the secondary consequences associated with TBI. Thus, examining pathophysiological changes from heterogeneous impacts is imperative for improving clinical translation and evaluating the efficacy of potential therapeutic strategies. Here we utilized TBI models that varied in both injury mechanism and severity including severe traditional controlled cortical impact (CCI), modified mild CCI (MTBI), and multiple severities of closed-head diffuse TBI (DTBI), and assessed pathophysiological changes. Severe CCI induced cortical lesions and necrosis, while both MTBI and DTBI lacked lesions or significant necrotic damage. Autophagy was activated in the ipsilateral cortex following CCI, but acutely impaired in the ipsilateral hippocampus. Additionally, autophagy was activated in the cortex following DTBI, and autophagic impairment was observed in either the cortex or hippocampus following impact from each DTBI severity. Thus, we provide evidence that autophagy is a therapeutic target for both mild and severe TBI. However, dramatic increases in necrosis following CCI may negatively impact the clinical translatability of therapeutics designed to treat acute dysfunction in TBI. Overall, these results provide evidence that injury sequalae affiliated with TBI heterogeneity is linked through autophagy activation and/or impaired autophagic flux. Thus, therapeutic strategies designed to intervene in autophagy may alleviate pathophysiological consequences, in addition to the cognitive and behavioral deficits observed in TBI.


Asunto(s)
Autofagia , Lesiones Traumáticas del Encéfalo , Modelos Animales de Enfermedad , Animales , Autofagia/fisiología , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/fisiopatología , Masculino , Muerte Celular/fisiología , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Ratas Sprague-Dawley , Ratas , Hipocampo/patología , Hipocampo/fisiopatología
9.
Bioact Mater ; 39: 14-24, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38783926

RESUMEN

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective ß-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

10.
Foods ; 13(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38611436

RESUMEN

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1ß, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

11.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38674153

RESUMEN

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.


Asunto(s)
Lesión Pulmonar Aguda , Lipopolisacáridos , Inhibidores de Serina Proteinasa , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Ratones , Inhibidores de Serina Proteinasa/farmacología , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Polietilenglicoles/química , Polietilenglicoles/farmacología , FN-kappa B/metabolismo , Masculino , Elastasa de Leucocito/metabolismo , Humanos , Transducción de Señal/efectos de los fármacos , Proteínas Recombinantes de Fusión/farmacología , Modelos Animales de Enfermedad
12.
Artículo en Inglés | MEDLINE | ID: mdl-38683722

RESUMEN

The fund investment industry heavily relies on the expertise of fund managers, who bear the responsibility of managing portfolios on behalf of clients. With their investment knowledge and professional skills, fund managers gain a competitive advantage over the average investor in the market. Consequently, investors prefer entrusting their investments to fund managers rather than directly investing in funds. For these investors, the primary concern is selecting a suitable fund manager. While previous studies have employed quantitative or qualitative methods to analyze various aspects of fund managers, such as performance metrics, personal characteristics, and performance persistence, they often face challenges when dealing with a large candidate space. Moreover, distinguishing whether a fund manager's performance stems from skill or luck poses a challenge, making it difficult to align with investors' preferences in the selection process. To address these challenges, this study characterizes the requirements of investors in selecting suitable fund managers and proposes an interactive visual analytics system called FMLens. This system streamlines the fund manager selection process, allowing investors to efficiently assess and deconstruct fund managers' investment styles and abilities across multiple dimensions. Additionally, the system empowers investors to scrutinize and compare fund managers' performances. The effectiveness of the approach is demonstrated through two case studies and a qualitative user study. Feedback from domain experts indicates that the system excels in analyzing fund managers from diverse perspectives, enhancing the efficiency of fund manager evaluation and selection.

13.
Ann Biomed Eng ; 52(6): 1693-1705, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38502430

RESUMEN

Convection-enhanced drug delivery (CED) directly infuses drugs with a large molecular weight toward target cells as a therapeutic strategy for neurodegenerative diseases and brain cancers. Despite the success of many previous in vitro experiments on CED, challenges still remain. In particular, a theoretical predictive model is needed to form a basis for treatment planning, and developing such a model requires well-controlled injection tests that can rigorously capture the convective (advective) and diffusive transport of an infusate. For this purpose, we investigated the advection-diffusion transport of an infusate (bromophenol blue solution) in the brain surrogate (0.2% w/w agarose gel) at different injection rates, ranging from 0.25 to 4 µL/min, by closely monitoring changes in the color intensity, propagation distance, and injection pressures. One dimensional closed-form solution was examined with two variable sets, such as the mathematically calculated coefficient of molecular diffusion and average velocity, and the hydraulic dispersion coefficient and seepage velocity by the least squared method. As a result, the seepage velocity was greater than the average velocity to some extent, particularly for the later infusion times. The poroelastic deformation in the brain surrogate might lead to changes in porosity, and consequently, slight increases in the actual flow velocity as infusion continues. The limitation of efficiency of the single catheter was analyzed by dimensionless analysis. Lastly, this study suggests a simple but robust approach that can properly capture the convective (advective) and diffusive transport of an infusate in an in vitro brain surrogate via well-controlled injection tests.


Asunto(s)
Encéfalo , Convección , Sistemas de Liberación de Medicamentos , Encéfalo/metabolismo , Azul de Bromofenol/farmacocinética , Azul de Bromofenol/administración & dosificación , Modelos Biológicos , Humanos , Difusión , Animales
14.
J Med Ext Real ; 1(1): 4-12, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38505474

RESUMEN

Medical extended reality (MXR) has emerged as a dynamic field at the intersection of health care and immersive technology, encompassing virtual, augmented, and mixed reality applications across a wide range of medical disciplines. Despite its rapid growth and recognition by regulatory bodies, the field lacks a standardized taxonomy to categorize its diverse research and applications. This American Medical Extended Reality Association guideline, authored by the editorial board of the Journal of Medical Extended Reality, introduces a comprehensive taxonomy for MXR, developed through a multidisciplinary and international collaboration of experts. The guideline seeks to standardize terminology, categorize existing work, and provide a structured framework for future research and development in MXR. An international and multidisciplinary panel of experts was convened, selected based on publication track record, contributions to MXR, and other objective measures. Through an iterative process, the panel identified primary and secondary topics in MXR. These topics were refined over several rounds of review, leading to the final taxonomy. The taxonomy comprises 13 primary topics that jointly expand into 180 secondary topics, demonstrating the field's breadth and depth. At the core of the taxonomy are five overarching domains: (1) technological integration and innovation; (2) design, development, and deployment; (3) clinical and therapeutic applications; (4) education, training, and communication; and (5) ethical, regulatory, and socioeconomic considerations. The developed taxonomy offers a framework for categorizing the diverse research and applications within MXR. It may serve as a foundational tool for researchers, clinicians, funders, academic publishers, and regulators, facilitating clearer communication and categorization in this rapidly evolving field. As MXR continues to grow, this taxonomy will be instrumental in guiding its development and ensuring a cohesive understanding of its multifaceted nature.

15.
Proc Natl Acad Sci U S A ; 121(14): e2321615121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38530892

RESUMEN

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.


Asunto(s)
Citrus , Citrus/química , Domesticación , Fitomejoramiento , Metilación , Metiltransferasas/metabolismo
16.
Adv Sci (Weinh) ; 11(14): e2306827, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38308184

RESUMEN

Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle-type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6-HMGCS1-YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non-alcoholic fatty liver diseases- associated HCC.


Asunto(s)
Carcinoma Hepatocelular , Hidroximetilglutaril-CoA Sintasa , Neoplasias Hepáticas , Proteínas Represoras , Proteínas Señalizadoras YAP , Humanos , Carcinoma Hepatocelular/metabolismo , Colesterol/metabolismo , Hidroximetilglutaril-CoA Sintasa/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Microambiente Tumoral , Ubiquitina/metabolismo , Proteínas Señalizadoras YAP/metabolismo
17.
Behav Brain Res ; 463: 114913, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38367773

RESUMEN

To assess the stability of electroencephalographic (EEG) spectral features across overnight polysomnography (PSG) and daytime multiple sleep latency tests (MSLTs) in chronic insomniacs (CIs) and normal controls (NCs). A total of 20 NCs and 22 CIs underwent standard PSG and MSLTs. Spectral analyses were performed on EEG data from PSG and MSLTs and absolute and relative power in central, frontal and occipital channels were obtained for wake (W) and non-rapid eye movement sleep stage 1 and 2 (N1, N2). Intraclass correlation coefficients (ICCs) were used to assess the stability of EEG spectral power across PSG and MSLTs for W, N1 and N2. The absolute power of all frequency bands except delta exhibited high stability across PSG and MSLTs in both NCs and CIs (ICCs ranged from 0.430 to 0.978). Although delta absolute power was stable in NCs during N1 and N2 stages (ICCs ranged from 0.571 to 0.835), it tended to be less stable in CIs during W and sleep stages (ICCs ranged from 0.042 to 0.807). We also observed lower stability of relative power compared to absolute power though the majority of relative power outcomes maintained high stability in both groups (ICCs in relative power ranged from 0.044 to 0.962). Most EEG spectral bandwidths across PSG and MSLT in W, N1 and N2 show high stability in good sleepers and chronic insomniacs. EEG signals from either an overnight PSG or a daytime MSLT may be useful for reliably exploring EEG spectral features during wakefulness or sleep.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Polisomnografía , Latencia del Sueño , Sueño , Fases del Sueño , Electroencefalografía
19.
Semin Dial ; 37(1): 43-51, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-36693653

RESUMEN

INTRODUCTION: Pulmonary hypertension (PH) is highly prevalent in patients receiving dialysis. The precise mechanisms underlying PH in hemodialysis (HD) patients have not been adequately addressed. Emerging experimental evidence indicates that circulating fibrocytes may contribute significantly to this process. METHODS: We measured the proportion of circulating fibrocytes using flow cytometry analysis and prospectively analyzed patients during HD from February 1, 2017, to February 1, 2022. Then we investigated correlations between circulating fibrocytes, inflammation cytokines, PH, and their affective factors that predict the prognosis of HD patients. RESULTS: The cohort included 192 patients. During a follow-up of 5 years, we registered 66 all-cause deaths, and 11 patients received kidney transplantation. The incidence of PH among HD patients was 30.9%. We found that the circulating fibrocyte level significantly correlated with pulmonary arterial systolic pressure (r = 0.412, p < 0.05). In the multiple logistic regression analysis, the percentage of circulating fibrocytes was an independent predictor of PH (odds ratio [OR]: 2.080, 95% confidence interval [CI]: 1.539-2.812, p < 0.001). Controlling for confounding covariates in the multivariate Cox regression models, the presence of PH conferred an increased risk of all-cause mortality in HD patients [hazard ratio (HR): 2.183, 95% CI:1.257-3.788, p = 0.006]. CONCLUSION: The prevalence of PH was high in HD patients and was associated with higher all-cause mortality. Higher circulating fibrocyte level was an independent predictor of the presence of PH; these fibrocytes may serve as early detection markers and novel therapeutic targets.


Asunto(s)
Hipertensión Pulmonar , Humanos , Hipertensión Pulmonar/etiología , Diálisis Renal/efectos adversos , Citometría de Flujo , Citocinas , Morbilidad
20.
Sleep ; 47(1)2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-37967212

RESUMEN

STUDY OBJECTIVES: This study explores polysomnographic and multiple sleep latency test (MSLT) differences between myotonic dystrophy type 1/type 2 (DM1/DM2) patients and controls. METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, All EBM databases, and Web of Science from inception to Aug 2023. RESULTS: Meta-analyses revealed significant reductions in sleep efficiency, N2 percentage, mean SpO2, and MSLT measured mean sleep latency, and increases in N3 sleep, wake time after sleep onset, apnea hypopnea index, and periodic limb movement index in DM1 patients compared with controls. However, any differences of polysomnographic sleep change between DM2 patients and controls could not be established due to limited available studies. CONCLUSIONS: Multiple significant polysomnographic abnormalities are present in DM1. More case-control studies evaluating polysomnographic changes in DM2 compared with controls are needed.


Asunto(s)
Distrofia Miotónica , Sueño de Onda Lenta , Humanos , Estudios de Casos y Controles , Polisomnografía , Sueño
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