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BACKGROUND: While circulating metabolites have been increasingly linked to cancer risk, the causality underlying these associations remains largely uninterrogated. METHODS: We conducted a comprehensive 2-sample Mendelian randomization (MR) study to evaluate the potential causal relationship between 913 plasma metabolites and the risk of seven cancers among European-ancestry individuals. Data on variant-metabolite associations were obtained from a genome-wide association study (GWAS) of plasma metabolites among 14,296 subjects. Data on variant-cancer associations were gathered from large-scale GWAS consortia for breast (N = 266,081), colorectal (N = 185,616), lung (N = 85,716), ovarian (N = 63,347), prostate (N = 140,306), renal cell (N = 31,190), and testicular germ cell (N = 28,135) cancers. MR analyses were performed with the inverse variance-weighted (IVW) method as the primary strategy to identify significant associations at Bonferroni-corrected P < 0.05 for each cancer type separately. Significant associations were subjected to additional scrutiny via weighted median MR, Egger regression, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and reverse MR analyses. Replication analyses were performed using an independent dataset from a plasma metabolite GWAS including 8,129 participants of European ancestry. RESULTS: We identified 94 significant associations, suggesting putative causal associations between 66 distinct plasma metabolites and the risk of seven cancers. Remarkably, 68.2% (45) of these metabolites were each associated with the risk of a specific cancer. Among the 66 metabolites, O-methylcatechol sulfate and 4-vinylphenol sulfate demonstrated the most pronounced positive and negative associations with cancer risk, respectively. Genetically proxied plasma levels of these two metabolites were significantly associated with the risk of lung cancer and renal cell cancer, with an odds ratio and 95% confidence interval of 2.81 (2.33-3.37) and 0.49 (0.40-0.61), respectively. None of these 94 associations was biased by weak instruments, horizontal pleiotropy, or reverse causation. Further, 64 of these 94 were eligible for replication analyses, and 54 (84.4%) showed P < 0.05 with association patterns consistent with those shown in primary analyses. CONCLUSIONS: Our study unveils plausible causal relationships between 66 plasma metabolites and cancer risk, expanding our understanding of the role of circulating metabolites in cancer genetics and etiology. These findings hold promise for enhancing cancer risk assessment and prevention strategies, meriting further exploration.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pulmonares , Masculino , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genéticaRESUMEN
In recent times, there has been a notable surge of interests in hafnia (HfO2)-based ferroelectrics, primarily due to their remarkable ferroelectric properties employed in ultra-thin configurations, alongside their compatibility with the conventional CMOS manufacturing process. In order to harness the full potential of HfO2-based films for high-performance non-volatile memory applications, it is imperative to enhance their ferroelectric characteristics and durability. This study introduces a straightforward approach aimed at augmenting the ferroelectric performance of HfxZr1-xO2(HZO) films deposited on silicon (Si) substrates through the engineering of oxygen vacancies (VO). The results of this endeavor demonstrate a significant enhancement in ferroelectric performance, characterized by a 2Pr value of 47µC cm-2and impressive endurance, enduring up to 108cycles under an 8 MV cm-1electric field without the need of a wake-up process. This marked improvement can be attributed to a dual-pronged approach, involving the incorporation of an Al2O3interlayer and the introduction of Al atoms into the HZO film. The Al2O3interlayer primarily serves to mitigate the presence of oxygen vacancies at the interface, while the introduction of Al dopants elevates the concentration of oxygen vacancies within the bulk material. This modulation of oxygen vacancy concentration proves instrumental in facilitating the formation of a ferroelectric o-III phase within the HZO-based films, thereby further augmenting their ferroelectric performance. This innovative and effective strategy offers an alternative avenue for enhancing the ferroelectric properties of materials characterized by a fluorite crystal structure.
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Glioma is characterized by rapid cell proliferation, aggressive invasion, altered apoptosis and a poor prognosis. ß-Sitosterol, a kind of phytosterol, has been shown to possess anticancer activities. Our current study aims to investigate the effects of ß-sitosterol on gliomas and reveal the underlying mechanisms. Our results show that ß-sitosterol effectively inhibits the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, ß-sitosterol inhibits migration by downregulating markers of epithelial-mesenchymal transition (EMT). Mechanistically, network pharmacology and transcriptomics approaches illustrate that the EGFR/MAPK signaling pathway may be responsible for the inhibitory effect of ß-sitosterol on glioma. Afterward, the results show that ß-sitosterol effectively suppresses the EGFR/MAPK signaling pathway. Moreover, ß-sitosterol significantly inhibits tumor growth in a U87 xenograft nude mouse model. ß-Sitosterol inhibits U87 cell proliferation and migration and induces apoptosis and cell cycle arrest in U87 cells by blocking the EGFR/MAPK signaling pathway. These results suggest that ß-sitosterol may be a promising therapeutic agent for the treatment of glioma.
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Glioma , Farmacología en Red , Sitoesteroles , Animales , Ratones , Humanos , Línea Celular Tumoral , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Transducción de Señal , Proliferación Celular , Receptores ErbB/genética , Receptores ErbB/metabolismo , Perfilación de la Expresión Génica , Apoptosis , Movimiento CelularRESUMEN
Despite the widespread investigations on the M-N-C type single atom catalysts (SACs) for oxygen evolution reaction (OER), an internal conflict between its intrinsic thermodynamically structural instability and apparent catalytic steadiness has long been ignored. Clearly unfolding this contradiction is necessary and meaningful for understanding the real structure-property relation of SACs. Herein, by using the well-designed pH-dependent metal leaching experiments and X-ray absorption spectroscopy, an unconventional structure reconstruction of M-N-C catalyst during OER process was observed. Combining with density functional theory calculations, the initial Ni-N coordination is easily broken in the presence of adsorbed OH*, leading to favorable formation of Ni-O coordination. The formed Ni-O works stably as the real active center for OER catalysis in alkaline media but unstably in acid, which clearly explains the existing conflict. Unveiling the internal contradiction between structural instability and catalytic steadiness provides valuable insights for rational design of single atom OER catalysts.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear. METHODS: In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings. RESULTS: In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-ß1 which activated the TGFßR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFß signaling inhibitor SB431542 or knockdown of TGFßR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-ß1. These patients also had worse prognoses and richer stemness markers. CONCLUSION: TGF-ß1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFß1-Smad2/3 pathway.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Línea Celular Tumoral , Proliferación CelularRESUMEN
An Ir(I)/squaramide cooperative catalytic strategy for atroposelective synthesis of axially chiral aryltriazoles has been developed for the first time. Diverse structurally novel aryltriazole skeletons that cannot be accessed by traditional click reactions were synthesized in good yields with excellent enantioselectivity. Both enantiomers were easily obtained from a pair of diastereoisomeric natural quinidine- and quinine-derived squaramides. A significant Ir(I)/squaramide coordination activation, but no self-quenching phenomenon was observed in this metal/organo cooperative catalytic system.
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Alquinos , Azidas , Catálisis , Reacción de Cicloadición , Quinina/análogos & derivados , EstereoisomerismoRESUMEN
A diamido-bridged dicobalt complex supported by a diamidonaphthalene ligand, Cp*2Co2(µ-1,8-C10H8(NH)2) (1), was synthesized, and the reactivity relevant to redox transformations of the Co2N2 core was investigated. It was found that the Co(II)-Co(II) bond allows for protonation by [HPPh3][BF4] resulting in a bridging hydride, [1H]+, with pKa â¼ 7.6 in CH2Cl2. The diamidonaphthalene ligand can stabilize the binuclear system in the Co(II)Co(III) mixed-valent state (1+), which is capable of binding CO to afford [1-CO]+. Surprisingly, the mixed-valent complex also activates H2O to furnish a Co(III)Co(III) hydroxy complex [1-OH]+ accompanied by release of H2. The hydroxy ligand in [1-OH]+ is exchangeable, as demonstrated by 18O-labeling experiments on [1-OH]+ with H218O that led to the heavier isotopolog [1-18OH]+.
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Oxygen diffusivity and surface exchange kinetics underpin the ionic, electronic, and catalytic functionalities of complex multivalent oxides. Towards understanding and controlling the kinetics of oxygen transport in emerging technologies, it is highly desirable to reveal the underlying lattice dynamics and ionic activities related to oxygen variation. In this study, the evolution of oxygen content is identified in real-time during the progress of a topotactic phase transition in La0.7 Sr0.3 MnO3-δ epitaxial thin films, both at the surface and throughout the bulk. Using polarized neutron reflectometry, a quantitative depth profile of the oxygen content gradient is achieved, which, alongside atomic-resolution scanning transmission electron microscopy, uniquely reveals the formation of a novel structural phase near the surface. Surface-sensitive X-ray spectroscopies further confirm a significant change of the electronic structure accompanying the transition. The anisotropic features of this novel phase enable a distinct oxygen diffusion pathway in contrast to conventional observation of oxygen motion at moderate temperatures. The results provide insights furthering the design of solid oxygen ion conductors within the framework of topotactic phase transitions.
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In the present work, millisecond-range flash lamp annealing is used to recrystallize Mn-implanted Ge. Through systematic investigations of structural and magnetic properties, we find that the flash lamp annealing produces a phase mixture consisting of spinodally decomposed Mn-rich ferromagnetic clusters within a paramagnetic-like matrix with randomly distributed Mn atoms. Increasing the annealing energy density from 46, via 50, to 56 J cm-2 causes the segregation of Mn atoms into clusters, as proven by transmission electron microscopy analysis and quantitatively confirmed by magnetization measurements. According to x-ray absorption spectroscopy, the dilute Mn ions within Ge are in d 5 electronic configuration. This Mn-doped Ge shows paramagnetism, as evidenced by the unsaturated magnetic-field-dependent x-ray magnetic circular dichroism signal. Our study reveals how spinodal decomposition occurs and influences the formation of ferromagnetic Mn-rich Ge-Mn nanoclusters.
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Aim: To provide clarity surrounding the association between tumor-associated macrophages (TAMs) and esophageal cancer prognosis. Materials & methods: Several databases were searched. The meta-analysis was conducted by using software Stata 12.0 and Revman. Results: Sixteen studies were included in this analysis (2292 samples). CD68+ TAM density was not associated with overall survival (OS; hazard ratio [HR]: 0.88, 95% CI: 0.67-1.15; p = 0.33) and disease-free survival (HR: 1.25, 95% CI: 0.66-2.35; p = 0.49). M2-like TAMs were associated with poor overall survival (HR: 1.47, 95% CI: 1.10-1.98; p = 0.01), Tumor, Node, Metastasis staging and vessel metastasis. Conclusion: CD68+ TAM density is not associated with esophageal cancer progression, while CD163+ M2-like TAMs is a potential risk factor.
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Neoplasias Esofágicas/metabolismo , Macrófagos/metabolismo , Pronóstico , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Supervivencia sin Enfermedad , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Humanos , Metástasis Linfática , Macrófagos/patología , Receptores de Superficie Celular/metabolismo , Microambiente Tumoral/genéticaRESUMEN
Influenza is an acute respiratory infectious disease caused by influenza viruses. Its subtype can be distinguished based on the antigenicity of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). One of the main challenges in anti-influenza drug development is the quick evolution of drug resistance due to virus mutations. One solution to this problem is to develop dual-targeting anti-influenza agents. In this paper, a new rationally designed virtual screening protocol that combines structure-based approaches (molecular docking and molecular dynamic simulations) and ligand-based approaches (support vector machines and 3D shape & electrostatic similarity algorithms) is reported for the virtual screening of dual-targeting agents against HA and NA. The final hits came from the consensus of the ligand- and receptor-based knowledge of HA and NA and were tested using ADMET predictions. Evidence from the binding energy calculations and binding mode analyses suggested that several of the hits are promising as dual-targeting anti-influenza agents. The virtual screening protocol may also lead to the identification of innovative drugs in other fields.
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Antivirales/química , Descubrimiento de Drogas/métodos , Glicoproteínas Hemaglutininas del Virus de la Influenza , Subtipo H5N1 del Virus de la Influenza A , Simulación de Dinámica Molecular , Neuraminidasa , Proteínas Virales , Antivirales/uso terapéutico , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/química , Neuraminidasa/metabolismo , Máquina de Vectores de Soporte , Proteínas Virales/antagonistas & inhibidores , Proteínas Virales/química , Proteínas Virales/metabolismoRESUMEN
INTRODUCTION: Peripheral vasodilation causes a redistribution of body temperature from the core to the periphery, resulting in shivering and hypothermia. These are normal pathological and physiological processes during spinal anaesthesia. Two drugs, norepinephrine and phenylephrine, have peripheral vasoconstrictive effects. It is unclear the effects of norepinephrine and phenylephrine on shivering and hypothermia in patients undergoing caesarean section under spinal anaesthesia. METHODS ANALYSIS: 240 eligible parturients will be recruited for this randomised, double-blind, controlled trial and randomly assigned to either the norepinephrine or phenylephrine groups. The primary outcome will be the incidence of shivering while secondary outcomes will include the severity of shivering, rectal temperature, incidence of hypothermia and umbilical artery blood pH value. ETHICS AND DISSEMINATION: The Institutional Ethics Committee of The Second People's Hospital of Hefei approved the trial protocol (ID: 2023-093). The results will be published in a compliant journal. The original data will be released in December 2029 on the ResMan original data-sharing platform of the China Clinical Trial Registry (http://www.medresman.org.cn). TRIAL REGISTRATION NUMBER: ChiCTR2300077164.
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Anestesia Raquidea , Cesárea , Hipotermia , Norepinefrina , Fenilefrina , Tiritona , Centros de Atención Terciaria , Humanos , Anestesia Raquidea/métodos , Anestesia Raquidea/efectos adversos , Tiritona/efectos de los fármacos , Cesárea/efectos adversos , Femenino , Método Doble Ciego , Embarazo , Norepinefrina/uso terapéutico , China/epidemiología , Hipotermia/prevención & control , Fenilefrina/uso terapéutico , Adulto , Anestesia Obstétrica/métodos , Anestesia Obstétrica/efectos adversos , Vasoconstrictores/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. METHODS: Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The "study drug" will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value. DISCUSSION: Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .
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Anestesia Obstétrica , Anestesia Raquidea , Cesárea , Norepinefrina , Fenilefrina , Ensayos Clínicos Controlados Aleatorios como Asunto , Vasoconstrictores , Humanos , Cesárea/efectos adversos , Anestesia Raquidea/efectos adversos , Femenino , Norepinefrina/sangre , Método Doble Ciego , Embarazo , Fenilefrina/administración & dosificación , Vasoconstrictores/uso terapéutico , Anestesia Obstétrica/efectos adversos , Anestesia Obstétrica/métodos , Adulto , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Factor VIII , Resultado del Tratamiento , Coagulación Sanguínea/efectos de los fármacos , Hemodinámica/efectos de los fármacosRESUMEN
Background: Emerging evidence points to the exceptional importance and value of m7G alteration in the diagnosis and prognosis of cancers. Nonetheless, a biomarker for precise screening of various cancer types has not yet been developed based on serum m7G-harboring miRNAs. Methods: A total of 20,702 serum samples, covering 12 cancer types and consisting of 7,768 cancer samples and 12,934 cancer-free samples were used in this study. A m7G target miRNA diagnostic signature (m7G-miRDS) was established through the least absolute shrinkage and selection operator (LASSO) analyses in a training dataset (n = 10,351), and validated in a validation dataset (n = 10,351). Results: The m7G-miRDS model, a 12 m7G-target-miRNAs signature, demonstrated high accuracy and was qualified for cancer detection. In the training and validation cohort, the area under the curve (AUC) reached 0.974 (95% CI 0.971-0.977) and 0.972 (95% CI 0.969-0.975), respectively. The m7G-miRDS showed superior sensitivity in each cancer type and had a satisfactory AUC in identifying bladder cancer, lung cancer and esophageal cancer. Additionally, the diagnostic performance of m7G-miRDS was not interfered by the gender, age and benign disease. Conclusion: Our results greatly extended the value of serum circulating miRNAs and m7G in cancer detection, and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as ncRNA modification.
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BACKGROUND: Venous thromboembolism (VTE) is one of the most common and serious complications of cesarean section in parturients. Norepinephrine (NE) has been shown to activate coagulation. The aim of this study was to compare the effect of a fixed-rate prophylactic norepinephrine infusion and a fixed-rate prophylactic phenylephrineï¼PHEï¼ infusion under spinal anesthesia for caesarean section on the prethrombotic response. MATERIALS AND METHODS: Sixty-six women undergoing cesarean section under spinal anesthesia were randomly assigned to the NE group or PHE group, starting simultaneously with the administration of the subarachnoid solution, a "study drug" solution containing either NE or PHE was pumped intravenously at a constant rate of 15 ml/h until the end of the operation. Plasma coagulation factor VIII activity (FVIII: C), Fibrinogen, and D-dimer levels were measured in blood samples obtained on admission to the operating theatre and at the end of the procedure. RESULTS: Compared with preoperative levels, there were no significant differences in postoperative fibrinogen and D-dimer levels in the NE group, except for a decrease in FVIII: C levels (P = 0.003). However, postoperative levels of FVIII: C (P = 0.009), fibrinogen (P = 0.035) and D-dimer (P = 0.025) were increased in the NE group compared with postoperative levels in the PHE group. CONCLUSIONS: NE does not affect the maternal prethrombotic response and can be safely used in cesarean sections. Compared with PHE infusion, NE infusion increased the level of coagulation molecules, suggesting that NE maybe more beneficial for women with high intraoperative bleeding requiring hemostasis.
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The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.
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Biomarcadores de Tumor , Islas de CpG , Metilación de ADN , Estudio de Asociación del Genoma Completo , Neoplasias , Especificidad de Órganos , Humanos , Islas de CpG/genética , Neoplasias/genética , Masculino , Femenino , Biomarcadores de Tumor/genética , Especificidad de Órganos/genética , Predisposición Genética a la Enfermedad , Regulación Neoplásica de la Expresión Génica , Epigénesis Genética , Neoplasias de Células Germinales y Embrionarias , Neoplasias TesticularesRESUMEN
Gut Universe Database (GutUDB) provides a comprehensive, systematic, and practical platform for researchers, and is dedicated to the management, analysis, and visualization of knowledge related to intestinal diseases. Based on this database, eight major categories of omics data analyses are carried out to explore the genotype-phenotype characteristics of a certain intestinal disease. The first tool for comprehensive omics data research on intestinal diseases will help each researcher better understand intestinal diseases.
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High-performance computing (HPC) has become a state strategic technology in a number of countries. One hypothesis is that HPC can accelerate biopharmaceutical innovation. Our experimental data demonstrate that HPC can significantly accelerate biopharmaceutical innovation by employing molecular dynamics-based virtual screening (MDVS). Without using HPC, MDVS for a 10K compound library with tens of nanoseconds of MD simulations requires years of computer time. In contrast, a state of the art HPC can be 600 times faster than an eight-core PC server is in screening a typical drug target (which contains about 40K atoms). Also, careful design of the GPU/CPU architecture can reduce the HPC costs. However, the communication cost of parallel computing is a bottleneck that acts as the main limit of further virtual screening improvements for drug innovations.
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Inhibidores de la Proteasa del VIH/química , Proteasa del VIH/química , Simulación de Dinámica Molecular , Neuraminidasa/química , PPAR alfa/química , Bibliotecas de Moléculas Pequeñas/química , Interfaz Usuario-Computador , Algoritmos , Inteligencia Artificial , Sitios de Unión , Bases de Datos de Compuestos Químicos , Bases de Datos de Proteínas , Descubrimiento de Drogas , Ensayos Analíticos de Alto Rendimiento/economía , Ensayos Analíticos de Alto Rendimiento/instrumentación , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Neuraminidasa/antagonistas & inhibidores , PPAR alfa/antagonistas & inhibidores , Unión Proteica , Relación Estructura-Actividad , TermodinámicaRESUMEN
Objectives: The available evidence on the connections between tooth loss, denture use, and mortality from all causes or specific causes among older adults is inconclusive. Therefore, we aimed to investigate the association between tooth loss, denture use, and all-cause and cause-specific mortality in older adults. Methods: A cohort of 5,403 participants aged 65 and older were recruited in the 2014 Chinese Longitudinal Healthy Longevity Survey wave and followed up in the 2018 wave. Cox proportional hazard models were used to examine the association between the number of natural teeth, denture use, and all-cause and cause-specific mortality. Results: During a mean (SD) follow-up of 3.1 years (1.3), 2,126 deaths (39.3%) occurred. Individuals with 0 and 1-9 teeth had higher mortality due to all-cause, cardiovascular disease (CVD), cancer, and other causes (all p-trend <0.05) than those with 20+ teeth. At the same time, no association was found with respiratory disease mortality. Participants who used dentures had lower mortality due to all causes [hazard ratios (HR) 0.79, 95% confidence intervals (CI) 0.71-0.88], CVD (HR 0.80, 95% CI 0.64-1.00), respiratory disease (HR 0.66, 95% CI 0.48-0.92), and other causes (HR 0.77, 95% CI 0.68-0.88) than those without dentures. Joint analysis revealed that older adults with fewer natural teeth and no dentures had higher mortality. Additionally, interaction analyses showed that the effects of the number of natural teeth on all-cause mortality were more pronounced in older adults aged <80 years (p-value for interaction = 0.03). Conclusion: Having fewer natural teeth, particularly less than 10 teeth, is linked to an increased risk of mortality from all causes, including CVD, cancer, and other causes, but not respiratory disease. The use of dentures would mitigate the adverse impact of tooth loss on all-cause and some cause-specific mortality.
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Enfermedades Cardiovasculares , Neoplasias , Pérdida de Diente , Humanos , Anciano , Pérdida de Diente/epidemiología , Pérdida de Diente/complicaciones , Estudios de Cohortes , Causas de Muerte , Neoplasias/complicacionesRESUMEN
[This corrects the article DOI: 10.3389/fpubh.2023.1194054.].