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1.
Nat Commun ; 15(1): 7961, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261474

RESUMEN

The efficient purification of cyclohexane is critical, serving as an essential feedstock to produce resins, nylon fibers and pharmaceutical intermediates. However, efficient purification remains a challenging task due to the similarity of cyclohexane and benzene molecules in terms of size and boiling point. In this work, we reported on the synergy of pore size and silanols inside an -SVR-type zeolite for the efficient production of ultrapure cyclohexane (benzene <1 ppm) from benzene/cyclohexane mixture. Under ambient conditions, the SSZ-74 zeolite demonstrated the highest mass-based productivity of 14.5 L/kg for ultrapure cyclohexane among several common zeolites with a considerable dynamic selectivity of ~9.5. The separation ability was evaluated through density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations. The unique ordered silanols inside the zeolite frameworks demonstrated strong but reversible interactions with benzene through SiOH…π interactions, as revealed by in situ Fourier Transform infrared (FTIR) spectra.

2.
J Am Chem Soc ; 146(38): 26379-26386, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39267584

RESUMEN

Breaking the trade-off between activity and stability of supported metal catalysts has been a long-standing challenge in catalysis, especially for metal nanoparticles (NPs) with high hydrogenation activity but poor stability. Herein, we report a porous poly(divinylbenzene) polymer-supported Pd NP catalyst (Pd/PDVB) with both high activity and excellent stability for the solvent-free hydrogenation of nitrobenzene, even at ambient temperature (25 °C) and H2 pressure (0.1 MPa). Pd/PDVB gave a turnover frequency as high as 22,632 h-1 at 70 °C and 0.4 MPa, exceeding 5556 h-1 of the classical Pd/C catalyst under equivalent conditions. Mechanistic studies reveal that the polymer support benefits the desorption of the aniline product from the Pd surface, which is crucial for rapid hydrogenation under solvent-free conditions. In addition, the polymer support in Pd/PDVB efficiently hindered Pd leaching, resulting in good stability.

3.
Front Neurosci ; 18: 1440756, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286478

RESUMEN

Aims: This study aims to systematically analyze the global trends in glioma methylation research using bibliometric methodologies. We focus on identifying the scholarly trajectory and key research interests, and we utilize these insights to predict future research directions within the epigenetic context of glioma. Methods: We performed a comprehensive literature search of the Web of Science Core Collection (WoSCC) to identify articles related to glioma methylation published from January 1, 2004, to December 31, 2023. The analysis included full-text publications in the English language and excluded non-research publications. Analysis and visualization were performed using GraphPad Prism, CiteSpace, and VOSviewer software. Results: The search identified 3,744 publications within the WoSCC database, including 3,124 original research articles and 620 review articles. The research output gradually increased from 2004 to 2007, followed by a significant increase after 2008, which peaked in 2022. A minor decline in publication output was noted during 2020-2021, potentially linked to the coronavirus disease 2019 pandemic. The United States and China were the leading contributors, collectively accounting for 57.85% of the total research output. The Helmholtz Association of Germany, the German Cancer Research Center (DKFZ), and the Ruprecht Karls University of Heidelberg were the most productive institutions. The Journal of Neuro-Oncology led in terms of publication volume, while Neuro-Oncology had the highest Impact Factor. The analysis of publishing authors revealed Michael Weller as the most prolific contributor. The co-citation network analysis identified David N. Louis's article as the most frequently cited. The keyword analysis revealed "temozolomide," "expression," "survival," and "DNA methylation" as the most prominent keywords, while "heterogeneity," "overall survival," and "tumor microenvironment" showed the strongest citation bursts. Conclusions: The findings of this study illustrate the increasing scholarly interest in glioma methylation, with a notable increase in research output over the past two decades. This study provides a comprehensive overview of the research landscape, highlighting the importance of temozolomide, DNA methylation, and the tumor microenvironment in glioma research. Despite its limitations, this study offers valuable insights into the current research trends and potential future directions, particularly in the realm of immunotherapy and epigenetic editing techniques.

4.
Chem Sci ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39246375

RESUMEN

A novel Ir-catalyzed asymmetric hydrogenation protocol for the synthesis of chiral tetrahydroquinoxaline (THQ) derivatives has been developed. By simply adjusting the reaction solvent, both enantiomers of mono-substituted chiral THQs could be selectively obtained in high yields with excellent enantioselectivities (toluene/dioxane: up to 93% yield and 98% ee (R); EtOH: up to 83% yield and 93% ee (S)). For 2,3-disubstituted chiral THQs, the cis-hydrogenation products were obtained with up to 95% yield, 20 : 1 dr, and 94% ee. Remarkably, this methodology was also applicable under continuous flow conditions, yielding gram-scale products with comparable yields and enantioselectivities (dioxane: 91% yield and 93% ee (R); EtOH: 90% yield and 87% ee (S)). Unlike previously reported Ir-catalyzed asymmetric hydrogenation protocols, this system exhibited a significant improvement as it required no additional additives. Furthermore, comprehensive mechanistic studies including deuterium-labeling experiments, control experiments, kinetic studies, and density functional theory (DFT) calculations were conducted to reveal the underlying mechanism of enantioselectivities for both enantiomers.

6.
Langmuir ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153002

RESUMEN

The interaction between Pt precursors and alumina support is an important step in synthesizing Pt/Al2O3 catalysts, while an in-depth understanding of the interaction is still lacking. Herein, density functional theory (DFT) calculations were performed to simulate the coordination of H2PtCl6 with different surface hydroxyl groups, revealing the influence of the γ-Al2O3 surface hydroxyl structure on the position of the Pt precursor and the removal of Cl ligands. After drying, the interaction mechanism between [PtCl6]2- and alumina support involves hydrogen bonds and van der Waals forces, which are the main driving forces for the structural transformation from [PtCl6]2- coordinated with the surface hydroxyl group into the PtClx(OH)y species (OH is the γ-Al2O3 surface group). HO-µ1-AlVI and H2O-µ1-AlVI on the (100) surface with electrophilicity facilitate hauling and activating the electron-rich [PtCl6]2-, but the nucleophilic (110) surface has a weaker interaction with [PtCl6]2-. Combining free energy and electronic property analysis, the stable structures on the (100) surface after drying treatment are PtCl4(OH)2 and PtCl3(OH)3, while only PtCl4(OH)2 structures can be formed on the (110) surface. This study can deepen our understanding of the interaction mechanism between Al-hydroxyl groups and Pt precursors, providing a theoretical reference for the precise placement of Pt active phases and the construction of metal-support interfaces.

7.
Chem Sci ; 15(31): 12316-12325, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39118604

RESUMEN

Purely organic room-temperature phosphorescence (RTP) has garnered substantial attention for its delayed emission, environmental sensitivity, and potential diverse applications. However, the quest for high-performance RTP materials has always been a challenge. In this study, we introduce novel weakly donor-acceptor (D-A) ternary π-conjugated architecture to construct an efficient RTP system. The strategy utilizes synergistic effects of the analogous El-Sayed rule, halogen-free heavy-atom effect, reduction of the singlet-triplet energy gap, and manipulation of flexible molecular conformation. A remarkable enhancement in the phosphorescence-to-fluorescence ratio was achieved, elevating from 0.4 in carbazole to 35.2 in DBTDBTCZ. Furthermore, the RTP system demonstrates single-component white luminescence, yielding warm and cool white colors. Intriguingly, we unveil the novel position-dependent heavy-atom effects, discerningly promoting intersystem crossing or phosphorescence decay. Benefiting from efficient RTP, multifunctional applications of real-time humidity monitoring, oxygen sensing, anti-counterfeiting labeling, and white lighting are demonstrated.

8.
Chem Sci ; 15(31): 12398-12409, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39118625

RESUMEN

Recognition of the intermediacy and regulation of reactivity patterns of radical intermediates in radical chemistry have profound impacts on harnessing and developing the full potential of open-shell species in synthetic settings. In this work, the possibility of in situ formation of O/N-X intermediates from Brønsted base covalently tethered carbonyl hypohalites (BCTCs) for the generation of heteroatom-centered radicals has certainly been excluded by NMR experiments and density functional theory calculations. Instead, the spectroscopic analyses reveal that the BCTCs serve as precursors of tether-tunable distonic radical anions (TDRAs) which have been unequivocally substantiated to be involved in the direct cleavage of O/N-H bonds to generate the corresponding heteroatom-centered radicals. Meanwhile, a deep insight into the properties and reactivities of the resulting TDRAs indicates that the introduction of a tethered Brønsted base on the parent open-shell species reinforces their stabilities and leads to a reversal of electrophilicity. Moreover, the dual descriptor values and electrophilicity indices are calculated based on eleven reported radical reactions involving various electrophilic/nucleophilic radical species, further confirming their validity in the prediction of the polar effect and the polarity-matching consistency between nucleophilic TDRAs and protic O/N-H bonds. The additional halogen-free experiments mediated by the combination of phthaloyl peroxide and TEMPO also prove the feasibility of the TDRA-assisted philicity-regulation approach. Lastly, detailed intrinsic bond orbital (IBO) and Hirschfeld spin population analyses are employed to elucidate that the H-atom abstraction processes are the polarity-matching proton-coupled electron transfer (PCET) pathways, with a degree of oxidative asynchronicity.

9.
Metab Brain Dis ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088109

RESUMEN

Alzheimer's disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aß) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aß plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aß plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.

10.
J Am Chem Soc ; 146(32): 22413-22423, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39096292

RESUMEN

Stereochemically pure saccharides have indispensable roles in fields ranging from medicinal chemistry to materials science and organic synthesis. However, the development of a simple, stereoselective, and efficient glycosylation protocol to access α- and ß-C-glycosides (particularly 2-deoxy entities) remains a persistent challenge. Existing studies have primarily focused on C1 modification of carbohydrates and transformation of glycosyl radical precursors. Here, we innovate by harnessing the in situ generated glycosyl-Ni species to achieve one-pot borylation and glycosylation in a cascade manner, which is enabled by an earth-abundant nickel-catalyzed carboboration of readily accessible glycals without any ligand. This work reveals the potential for the development of a modular and multifunctional glycosylation platform to facilitate the simultaneous introduction of C-C and C-B bonds at the stereogenic center of saccharides, a largely unexploited research area. Preliminary experimental and computational studies indicate that the endocyclic O and the C3 group play important roles in stereoseclectively forging glycosidic bonds. As a result, a diverse range of C-R (R = alkyl, aryl, and alkenyl) and 2-deoxygenated glycosides bearing modifiable boron groups could be rapidly made with excellent stereocontrol and exhibit remarkable functional group tolerance. The synthetic potential is underscored in the late-stage glycosylation of natural products and commercial drugs as well as the facile preparation of various rare sugars, bioactive conjugates, and key intermediates to prorocentin, phomonol, and aspergillide A.

11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(7): 648-654, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39179409

RESUMEN

Ischemic stroke is one of the diseases which pose a significant threat to human health. Recent studies have suggested that programmed cell death plays an important role in brain tissues affected by ischemia and hypoxia. Pyroptosis, which is characterized by both apoptosis and necrosis, is mediated by activation of inflammasomes, such as NOD-like receptor family, pyrin domain containing 3 (NLRP3). Pyroptosis, which depends on caspase-1 activation and the release of pro-inflammatory cytokines, such as Interleukin 1ß and Interleukin 18, plays a vital role in regulating cell survival and death following ischemic injury. Previous studies have shown that pyroptosis is closely related to the activation of the NLRP3 inflammasome in ischemic stroke tissues. This distinctive form of cell death mainly occurs in microglia, neurons, astrocytes and endothelial cells. This paper reviews the role of pyroptosis mediated by inflammasomes in ischemic stroke, discussing the targets and substances that affect the activation of the NLRP3 inflammasome, which can provide a new theoretical and experimental basis for the treatment of ischemic stroke.


Asunto(s)
Inflamasomas , Accidente Cerebrovascular Isquémico , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Humanos , Inflamasomas/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología
12.
J Hazard Mater ; 478: 135394, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39128148

RESUMEN

Evidence of the associations between long-term exposure to PM2.5 and O3 and human blood lipid concentrations is abundant yet inconclusive. Whether clean air policies could improve lipid profiles remains unclear. In total, 2979312 participants from a Chinese nationwide prospective study were included. For cross-sectional analyses, linear mixed-effects models were utilized to assess the associations of pollutants with lipid profiles (TC, LDL-C, TG, HDL-C). For longitudinal analyses, a quasi-experimental design and difference-in-differences models were employed to investigate the impact of China's Clean Air Act. In the cross-sectional analyses, each IQR increase in PM2.5 was associated with 2.49 % (95 % CI: 2.36 %, 2.62 %), 2.51 % (95 % CI: 2.26 %, 2.75 %), 3.94 % (95 % CI: 3.65 %, 4.23 %), and 1.54 % (95 % CI: 1.38 %, 1.70 %) increases in TC, LDL-C, TG, and HDL-C, respectively. For each IQR increase in O3, TC, LDL-C, TG, and HDL-C changed by 1.06 % (95 % CI: 0.95 %, 1.17 %), 1.21 % (95 % CI: 1.01 %, 1.42 %), 1.78 % (95 % CI: 1.54 %, 2.02 %), and -0.63 % (95 % CI: -0.76 %, -0.49 %), respectively. Longitudinal analyses showed that the intervention group experienced greater TC, LDL-C, and HDL-C reductions (1.77 %, 4.26 %, and 7.70 %, respectively). Our findings suggest that clean air policies could improve lipid metabolism and should be implemented in countries with heavy air pollution burdens.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Lípidos , Material Particulado , Humanos , China , Masculino , Femenino , Persona de Mediana Edad , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , Adulto , Lípidos/sangre , Estudios Transversales , Ozono/análisis , Estudios Prospectivos , Aterosclerosis/prevención & control , Aterosclerosis/sangre , Anciano , Estudios Longitudinales , Exposición a Riesgos Ambientales
13.
Chin Med J (Engl) ; 137(17): 2075-2083, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39075633

RESUMEN

BACKGROUND: The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups. METHODS: A total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014-2019) were included. Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories (<70.0, 70.0-99.9, 100.0-129.9 [reference group], 130.0-159.9, 160.0-189.9, and ≥190.0 mg/dL) and all-cause and cause-specific mortality. RESULTS: During a median follow-up of 3.7 years, 57,391 and 23,241 deaths from all-cause and overall CVD were documented. We observed J-shaped associations between LDL-C and death from all-cause, overall CVD, coronary heart disease (CHD), and ischemic stroke, and an L-shaped association between LDL-C and hemorrhagic stroke (HS) mortality ( P for non-linearity <0.001). Compared with the reference group (100.0-129.9 mg/dL), very low LDL-C levels (<70.0 mg/dL) were significantly associated with increased risk of overall CVD (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.06-1.14) and HS mortality (HR: 1.37, 95% CI: 1.29-1.45). Very high LDL-C levels (≥190.0 mg/dL) were associated with increased risk of overall CVD (HR: 1.51, 95% CI: 1.40-1.62) and CHD mortality (HR: 2.08, 95% CI: 1.92-2.24). The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age, low or normal body mass index, low or moderate 10-year atherosclerotic CVD risk, and those without diagnosed CVD or taking statins. Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people. CONCLUSIONS: People with very low LDL-C had a higher risk of all-cause, CVD, and HS mortality; those with very high LDL-C had a higher risk of all-cause, CVD, and CHD mortality. On the basis of our findings, comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.


Asunto(s)
Enfermedades Cardiovasculares , LDL-Colesterol , Modelos de Riesgos Proporcionales , Humanos , Persona de Mediana Edad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , LDL-Colesterol/sangre , Masculino , Femenino , Adulto , Anciano , Estudios de Cohortes , Factores de Riesgo , China/epidemiología
14.
J Am Chem Soc ; 146(28): 19070-19076, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38968610

RESUMEN

Catalysis plays a pivotal role in both chemistry and biology, primarily attributed to its ability to stabilize transition states and lower activation free energies, thereby accelerating reaction rates. While computational studies have contributed valuable mechanistic insights, there remains a scarcity of experimental investigations into transition states. In this work, we embark on an experimental exploration of the catalytic energy lowering associated with transition states in the photorearrangement of the phenylperoxy radical-water complex to the oxepin-2(5H)-one-5-yl radical. Employing matrix isolation spectroscopy, density functional theory, and post-HF computations, we scrutinize the (photo)catalytic impact of a single water molecule on the rearrangement. Our computations indicate that the barrier heights for the water-assisted unimolecular isomerization steps are approximately 2-3 kcal mol-1 lower compared to the uncatalyzed steps. This decrease directly coincides with the energy difference in the required wavelength during the transformation (Δλ = λ546 nm - λ579 nm ≡ 52.4-49.4 = 3.0 kcal mol-1), allowing us to elucidate the differential transition state energy in the photochemical rearrangement of the phenylperoxy radical catalyzed by a single water molecule. Our work highlights the important role of water catalysis and has, among others, implications for understanding the mechanism of organic reactions under atmospheric conditions.

15.
Org Lett ; 26(27): 5844-5849, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38950387

RESUMEN

We have developed a highly regio-, diastereo-, and enantioselective Cu-catalyzed desymmetrization of inert meso-diethers using Grignard reagents. Moreover, previous inaccessible sterically hindered organometallic reagents are realized in the reaction with broad secondary alkyl Grignard reagents. Finally, detailed control experiments and density functional theory calculations revealed the desymmetrization of meso-diethers exploits a direct anti-SN2' pathway, in the absence of an in situ-generated allyl bromine intermediate. The following oxidative addition is the crucial rate-determining and enantioselectivity-determining step.

16.
Lancet Reg Health West Pac ; 49: 101135, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39050982

RESUMEN

Background: The triglyceride-glucose (TyG) index has been recognized as a crucial risk factor for cardiovascular diseases. However, the association between the TyG index and mortality in the general population remains elusive. Methods: Participants were enrolled from the China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART), a nationwide prospective cohort study. The outcomes of interest were all-cause, cardiovascular, and cancer mortality. Restricted cubic splines and Cox regression models were used to assess the associations between the TyG index and outcomes. Findings: In total, 3,524,459 participants with a median follow-up of 4.6 (IQR, 3.1-5.8) years were included. The associations of the TyG index with all-cause and cardiovascular mortality were reverse L-shaped, with cut-off values of 9.75 for all-cause mortality and 9.85 for cardiovascular mortality. For each 1-unit increase in the TyG index, when below the cut-off values, the TyG index was not significantly associated with all-cause mortality (HR = 1.02, 95% CI: 1.00-1.03) and was only modestly associated with cardiovascular mortality (HR = 1.09, 95% CI: 1.06-1.11). Conversely, when the cut-off values were exceeded, the HRs (95% CI) were 2.10 (1.94-2.29) for all-cause mortality and 1.99 (1.72-2.30) for cardiovascular mortality. However, the association between the TyG index and cancer mortality was linearly negative (HR = 0.97, 95% CI: 0.94-0.99). Interpretation: The associations of the TyG index with all-cause and cardiovascular mortality displayed reverse L-shaped patterns, while an elevated TyG index showed a slight negative association with cancer mortality. We suggest that <9.75 could be the optimal TyG index cut-off value among the Chinese general population. Individuals at high risk of mortality might benefit from proper management of a high TyG index. Funding: The National High Level Hospital Clinical Research Funding (2023-GSP-ZD-2, 2023-GSP-RC-01), the Ministry of Finance of China and National Health Commission of China.

17.
JAMA Netw Open ; 7(7): e2422558, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023892

RESUMEN

Importance: Limited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications. Objective: To explore the associations between LDL-C levels and mortality and to identify the optimal ranges of LDL-C with the lowest risk of mortality in populations with diverse ASCVD risk profiles. Design, Setting, and Participants: The ChinaHEART project is a prospective cohort study that recruited residents aged 35 to 75 years from 31 provinces in mainland China between November 2014 and December 2022. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts on the basis of their medical history and ASCVD risk. Data analysis was performed from December 2022 to October 2023. Main Outcomes and Measures: The primary end point was all-cause mortality, and secondary end points included cause-specific mortality. Mortality data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed by using Cox proportional hazard regression models with various adjusted variables. Results: A total of 4 379 252 individuals were recruited, and 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) were included in the current study. The median (IQR) LDL-C concentration was 93.1 (70.9-117.3) mg/dL overall at baseline. During a median (IQR) follow-up of 4.6 (3.1-5.8) years, 92 888 deaths were recorded, including 38 627 cardiovascular deaths. The association between LDL-C concentration and all-cause or cardiovascular disease (CVD) mortality was U-shaped in both the low-risk cohort (2 838 354 participants) and the primary prevention cohort (829 567 participants), whereas it was J-shaped in the secondary prevention cohort (121 104 participants). The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C concentration associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87 mg/dL vs 114.6 mg/dL) were both lower in individuals with diabetes than in individuals without diabetes in the overall cohort. Conclusions and Relevance: This study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes.


Asunto(s)
Enfermedades Cardiovasculares , LDL-Colesterol , Humanos , Persona de Mediana Edad , Femenino , Masculino , LDL-Colesterol/sangre , China/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Anciano , Adulto , Estudios Prospectivos , Factores de Riesgo , Medición de Riesgo/métodos , Modelos de Riesgos Proporcionales , Factores de Riesgo de Enfermedad Cardiaca
18.
Front Oncol ; 14: 1360404, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903708

RESUMEN

Background: This study analyzed the risk factors associated with positive surgical margins (PSM) and five-year survival after prostate cancer resection to construct a positive margin prediction model. Methods: We retrospectively analyzed the clinical data of 148 patients treated with prostatectomy. The patients were divided into PSM group and Negative surgical margins (NSM) group. Several parameters were compared between the groups. All patients were followed up for 60 months. The risk factors for PSM and five-year survival were evaluated by univariate analysis, followed by multifactorial dichotomous logistic regression analysis. Finally, ROC curves were plotted for the risk factors to establish a predictive model for PSM after prostate cancer resection. Results: (1) Serum PSA, percentage of positive puncture stitches, clinical stage, surgical approach, Gleason score on puncture biopsy, and perineural invasion were significantly associated with the risk of PSM (P < 0.05). Serum PSA, perineural invasion, Gleason score on puncture biopsy, and percentage of positive puncture stitches were independent risk factors for PSM. (2) Total prostate-specific antigen (tPSA) by puncture, nutritional status, lymph node metastasis, bone metastasis, and seminal vesicle invasion may be risk factors for five-year survival. Lymph node metastasis and nutritional status were the main risk factors for the five-year survival of patients with prostate cancer. (3) After plotting the ROC curve, the area under the curve (AUC) [AUC: 0.776, 95%, confidence interval (CI): 0.725 to 0.854] was found to be a valid predictor of PSM; the AUC [AUC: 0.664, 95%, confidence interval (CI): 0.576 to 0.753] was also a valid predictor of five-year survival (P < 0.05). (4) The scoring system had a standard error of 0.02 and a cut-off value of 6. It predicted PSM after prostate cancer resection with moderate efficacy. Conclusions: Serum PSA, perineural invasion, puncture biopsy Gleason score, and percentage of positive puncture stitches were independent risk factors for positive surgical margins (PSM). Also, lymph node metastasis and nutritional status were the main risk factors for the five-year survival of patients with prostate cancer. Overall, the prediction efficacy of this scoring system concerning the risk of PSM after prostate cancer resection was moderate.

19.
Physiol Meas ; 45(5)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38722551

RESUMEN

Objective. Snoring is the most typical symptom of obstructive sleep apnea hypopnea syndrome (OSAHS) that can be used to develop a non-invasive approach for automatically detecting OSAHS patients.Approach. In this work, a model based on transfer learning and model fusion was applied to classify simple snorers and OSAHS patients. Three kinds of basic models were constructed based on pretrained Visual Geometry Group-16 (VGG16), pretrained audio neural networks (PANN), and Mel-frequency cepstral coefficient (MFCC). The XGBoost was used to select features based on feature importance, the majority voting strategy was applied to fuse these basic models and leave-one-subject-out cross validation was used to evaluate the proposed model.Main results. The results show that the fused model embedded with top-5 VGG16 features, top-5 PANN features, and MFCC feature can correctly identify OSAHS patients (AHI > 5) with 100% accuracy.Significance. The proposed fused model provides a good classification performance with lower computational cost and higher robustness that makes detecting OSAHS patients at home possible.


Asunto(s)
Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Automatización , Masculino , Redes Neurales de la Computación , Persona de Mediana Edad , Adulto , Femenino , Procesamiento de Señales Asistido por Computador , Ronquido/diagnóstico , Ronquido/fisiopatología
20.
Plant Physiol ; 196(1): 511-534, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-38748600

RESUMEN

Increasing the amount of cellular space allocated to plastids will lead to increases in the quality and yield of crop plants. However, mechanisms that allocate cellular space to plastids remain poorly understood. To test whether the tomato (Solanum lycopersicum L.) REDUCED CHLOROPLAST COVERAGE (SlREC) gene products serve as central components of the mechanism that allocates cellular space to plastids and contribute to the quality of tomato fruit, we knocked out the 4-member SlREC gene family. We found that slrec mutants accumulated lower levels of chlorophyll in leaves and fruits, accumulated lower levels of carotenoids in flowers and fruits, allocated less cellular space to plastids in leaf mesophyll and fruit pericarp cells, and developed abnormal plastids in flowers and fruits. Fruits produced by slrec mutants initiated ripening later than wild type and produced abnormal levels of ethylene and abscisic acid (ABA). Metabolome and transcriptome analyses of slrec mutant fruits indicated that the SlREC gene products markedly influence plastid-related gene expression, primary and specialized metabolism, and the response to biotic stress. Our findings and previous work with distinct species indicate that REC proteins help allocate cellular space to plastids in diverse species and cell types and, thus, play a central role in allocating cellular space to plastids. Moreover, the SlREC proteins are required for the high-level accumulation of chlorophyll and carotenoids in diverse organs, including fruits, promote the development of plastids and influence fruit ripening by acting both upstream and downstream of ABA biosynthesis in a complex network.


Asunto(s)
Carotenoides , Cloroplastos , Frutas , Regulación de la Expresión Génica de las Plantas , Plastidios , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Solanum lycopersicum/crecimiento & desarrollo , Carotenoides/metabolismo , Plastidios/metabolismo , Plastidios/genética , Frutas/metabolismo , Frutas/genética , Frutas/crecimiento & desarrollo , Cloroplastos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Mutación/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Clorofila/metabolismo , Ácido Abscísico/metabolismo , Proteínas de Cloroplastos/metabolismo , Proteínas de Cloroplastos/genética , Etilenos/metabolismo , Flores/genética , Flores/metabolismo , Flores/crecimiento & desarrollo
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