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Per- and polyfluoroalkyl substances (PFAS), known as "forever chemicals," are synthetic chemicals which have been used since the 1940s. Given their remarkable thermostability and chemical stability, PFAS have been widely utilized in commercial products, including textiles, surfactants, food packages, nonstick coatings, and fire-fighting foams. Thus, PFAS are widely distributed worldwide and have been detected in human urine, blood, breast milk, tissues and other substances. Growing concerns over the risks of PFAS, including their toxicity and carcinogenicity, have attracted people's attention. Recent reviews have predominantly emphasized advancements in the detection, adsorption, and degradation of PFAS through their chemical structures and toxic properties; however, further examination of the literature is needed to determine the link between PFAS exposure and cancer risk. Here, we introduced different PFAS detection methods based on sensors and liquid chromatography-mass spectrometry (LC-MS). Then, we discussed epidemiological investigations on PFAS levels and cancer risks in recent years, as well as the mechanisms underlying the carcinogenesis. Finally, we proposed the "4C principles" for ongoing exploration and refinement in this field. This review highlights PFAS-cancer associations to fill knowledge gaps and provide evidence-based strategies for future research.
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Lithium-oxygen batteries (LOBs) have been widely studied because of their ultra-high energy density (â¼3500 Wh kg-1). However, the reversibility and stability of LOBs are greatly limited by the sluggish kinetics of oxygen reduction/evolution reactions (ORR/OER) and severely parasitic reactions on oxygen electrodes. Electrolyte in LOBs plays an important role in the transport of reactive oxygen species and Li+, which greatly affects the kinetics and reversibility of the charging and discharging processes of batteries. In this work, perfluorooctane (PFO) is used as the additive in 1.0 M LiTFSI/TEGDEM electrolyte for LOBs to regulate the kinetics of oxygen electrode reactions. Due to the strong adsorption ability of PE toward oxygen, the oxygen concentration inside the electrolyte is greatly increased after the addition of PE. In addition, the PE-added electrolyte also exhibits superior electrochemical stability and is capable of triggering solution-mediated Li2O2 growth pathway during the discharge process of the LOBs. Therefore, with the increased oxygen concentration and the optimized electrode/electrolyte interface, the ORR/OER kinetics on the oxygen electrode is significantly promoted, which enables the LOBs with excellent energy efficiency and cycling life. This work provides a new idea for the design of oxygen-rich and high-performance electrolyte for lithium-oxygen batteries.
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The flotation separation of galena from sphalerite was commonly implemented under pH > 10.5, which led to the consumption of lime. In this paper, 2-diethylamine-4-hydroxy-1,3,5-triazine-6-thiol (DEHTT) was synthesized and introduced as a highly selective collector to perform the depressant-free flotation separation of Pb/Zn sulfide minerals. The microflotation results indicated that 8.0 × 10-7 mol/L DEHTT recovered 94.17% galena and 26.67% sphalerite from their mixture at pH 8.5 regulated by Na2CO3, and under the same conditions, sodium isobutyl xanthate (SIBX) floated out 94.94% galena and 50.41% sphalerite, deducing a superior flotation selectivity of DEHTT in comparison to SIBX. In situ AFM images displayed the more preferable adsorption of DEHTT on galena in comparison to that on sphalerite. The results of adsorption thermodynamics and kinetics inferred that the adsorption of DEHTT onto the galena surface was a spontaneous endothermic chemical process. XPS further indicated that DEHTT combined with interface Pb atoms to form the -S-Pb and -O-Pb bonds. The special affinity of DEHTT to galena achieved the selective flotation separation of galena from sphalerite without the addition of lime and depressants.
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BACKGROUND: To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. METHODS: We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. RESULTS: Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. CONCLUSIONS: Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.
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Optoelectronic synapses, leveraging the integration of classic photo-electric effect with synaptic plasticity, are emerging as building blocks for artificial vision and photonic neuromorphic computing. However, the fundamental working principles of most optoelectronic synapses mainly rely on physical behaviors while missing chemical-electric synaptic processes critical for mimicking biorealistic neuromorphic functionality. Herein, we report a photoelectrochemical synaptic device based on p-AlGaN/n-GaN semiconductor nanowires to incorporate chemical-electric synaptic behaviors into optoelectronic synapses, demonstrating unparalleled dual-modal plasticity and chemically-regulated neuromorphic functions through the interplay of internal photo-electric and external electrolyte-mediated chemical-electric processes. Electrical modulation by implementing closed or open-circuit enables switching of optoelectronic synaptic operation between short-term and long-term plasticity. Furthermore, inspired by transmembrane receptors that connect extracellular and intracellular events, synaptic responses can also be effectively amplified by applying chemical modifications to nanowire surfaces, which tune external and internal charge behaviors. Notably, under varied external electrolyte environments (ion/molecule species and concentrations), our device successfully mimics chemically-regulated synaptic activities and emulates intricate oxidative stress-induced biological phenomena. Essentially, we demonstrate that through the nanowire photoelectrochemical synapse configuration, optoelectronic synapses can be incorporated with chemical-electric behaviors to bridge the gap between classic optoelectronic synapses and biological synapses, providing a promising platform for multifunctional neuromorphic applications.
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OBJECTIVE: To explore the diagnostic value of nanopore sequencing technology for detecting nontuberculous mycobacterial pulmonary disease (NTM-PD) in bronchial alveolar lavage fluid (BALF). METHODS: A retrospective analysis was conducted on 83 patients with suspected NTM-PD admitted to Anhui Chest Hospital from January 2021 to November 2023. All patients underwent bronchoscopic examination, and BALF samples were collected for smear acid-fast staining, mycobacterial culture, and nanopore sequencing. The diagnostic efficiencies of these three methods were compared. RESULTS: Among these patients, 27 were diagnosed with NTM-PD, 43 with pulmonary tuberculosis (PTB), and 13 with other lung diseases (OLD). The sensitivity, specificity, positive and negative predictive value of nanopore sequencing for diagnosing NTM-PD were 88.9%, 87.5%, 77.4%, and 94.2%, respectively. Nanopore sequencing demonstrated significantly higher sensitivity than smear and culture methods. The area under the receiver operating characteristic (ROC) curve (AUC) for nanopore sequencing was 0.882, significantly higher than that of smear (0.547) and culture (0.658), with P values less than 0.05. CONCLUSION: Nanopore sequencing technology has high diagnostic efficiency for NTM-PD and can directly identify bacterial species, but specificity issues should be considered in clinical application.
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Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.
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OBJECTIVE: Non-cirrhotic porto-mesenteric vein thrombosis (NC-PMVT) is a rare but severe clinical condition. The study aims to assess the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) coupled with dual-access thrombolysis in patients with acute severe NC-PMVT. METHODS: From January 2018 to February 2023, a total of 25 patients with acute severe NC-PMVT who were treated with TIPS in conjunction with mechanical thrombectomy and dual-access thrombolysis. The period of thrombolysis was determined by the improvement of clinical symptoms and vascular recanalization. The technical success, recanalization rate, clinical success, and procedure-related complications were analyzed. RESULTS: The technical success rate was 100 %. The median duration for thrombolytic catheter removal was 5 (IQR 3.5 - 7) days. Full and partial recanalization were accomplished in 10 (40 %) and 15 (60 %) patients respectively before discharge. No significant procedure-related complications were reported. The clinical success rate was 88 %, with a mortality rate of 12 %. Over a median follow-up of 8 months, 3/22 (13.64 %) patients had a recurrence of thrombosis; 1/22 (4.54 %) patients underwent partial intestinal resection one and a half months post-discharge; the remaining patients did not experience any portal hypertensive complications. CONCLUSION: The combination of TIPS and dual-access thrombolysis appears to be safe and effective for patients with acute severe NC-PMVT.
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A metal surface with controllable infrared emissivity has a wide range of applications. However, a flexible and simple fabrication method is needed. Here, a controllable femtosecond laser self-deposition technology was developed to fabricate Al@AlOx core/shell micropillars (MPs) with diverse size distribution on the aluminum surface in a single-step operation under ambient conditions. By establishing a deterministic relationship between pulse-repetition frequency (PRF) and particle size distribution (PSD), we achieved continuous control of the infrared emissivity of the surface by lower PRF, ranging from low (0.31) to high (0.93). Additionally, by using higher PRF, we attained dual-band emissivity control, featuring high emissivity in the range of 10-14â µm and near-continuous change in the range of 2.5-10â µm.
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Reported here is a rapid and versatile synthetic approach towards the specific pentacyclic carbazolelactams related to calothrixin B. The crucial transformation is an acid-promoted cascade involving a dehydration/electrocyclization/C-N bond cleavage/lactamization sequence.
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Inflammatory bowel diseases (IBDs) are chronic, relapsing, and inflammatory disorders of the gastrointestinal tract characterized by abnormal immune responses. Recently, STING has emerged as a promising therapeutic target for various autoinflammatory diseases. However, few STING-selective small molecules have been investigated as novel strategies for IBD. In this study, we sought to examine the effects of PROTAC-based STING degrader SP23 on acute colitis and explore its underlying mechanism. SP23 treatment notably alleviates dextran sulfate sodium (DSS)-induced colitis. Pharmacological degradation of STING significantly reduced the production of inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, and inhibited macrophage polarization towards the M1 type. Furthermore, SP23 administration decreased the loss of tight junction proteins, including ZO-1, occludin, and claudin-1, and downregulated STING and NLRP3 signaling pathways in intestinal inflammation. In vitro, STING activated NLRP3 inflammasome-mediated pyroptosis in intestinal epithelial cells, which could be abrogated by SP23 and STING siRNA intervention. In conclusion, these findings provide new evidence for STING as a novel therapeutic target for IBD, and reveal that hyperactivation of STING could exaggerate colitis by inducing NLRP3/Caspase-1/GSDMD axis mediated intestinal epithelial cells pyroptosis.
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Colitis , Sulfato de Dextran , Macrófagos , Proteínas de la Membrana , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Piroptosis/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Transducción de Señal/efectos de los fármacos , Inflamasomas/metabolismo , Citocinas/metabolismo , Masculino , Humanos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Modelos Animales de Enfermedad , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
PURPOSE: Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes. METHODS: Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values. FINDINGS: GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours. IMPLICATIONS: This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.
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The research analyzed the effect of weekly training plans, physical training frequency, AI-powered coaching systems, virtual reality (VR) training environments, wearable sensors on developing technical tennis skills, with and personalized learning as a mediator. It adopted a quantitative survey method, using primary data from 374 young tennis players. The model fitness was evaluated using confirmatory factor analysis (CFA), while the hypotheses were evaluated using structural equation modeling (SEM). The model fitness was confirmed through CFA, demonstrating high fit indices: CFI = 0.924, TLI = 0.913, IFI = 0.924, RMSEA = 0.057, and SRMR = 0.041, indicating a robust model fit. Hypotheses testing revealed that physical training frequency (ß = 0.198, p = 0.000), AI-powered coaching systems (ß = 0.349, p = 0.000), virtual reality training environments (ß = 0.476, p = 0.000), and wearable sensors (ß = 0.171, p = 0.000) significantly influenced technical skills acquisition. In contrast, the weekly training plan (ß = 0.024, p = 0.834) and personalized learning (ß = -0.045, p = 0.81) did not have a significant effect. Mediation analysis revealed that personalized learning was not a significant mediator between training methods/technologies and acquiring technical abilities. The results revealed that physical training frequency, AI-powered coaching systems, virtual reality training environments, and wearable sensors significantly influenced technical skills acquisition. However, personalized learning did not have a significant mediation effect. The study recommended that young tennis players' organizations and stakeholders consider investing in emerging technologies and training methods. Effective training should be given to coaches on effectively integrating emerging technologies into coaching regimens and practices.
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Tenis , Humanos , Tenis/educación , Masculino , Femenino , Adolescente , Realidad Virtual , Niño , Rendimiento Atlético/fisiología , Aprendizaje , Dispositivos Electrónicos VestiblesRESUMEN
OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.
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BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for â¼60% of CPVT patients which is inherited in an autosomal dominant pattern. OBJECTIVE: This study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. METHODS: Clinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. RESULTS: This is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). CONCLUSION: The discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.
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Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.
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Autofagia , Degeneración del Disco Intervertebral , Nanopartículas , Ratas Sprague-Dawley , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Animales , Autofagia/efectos de los fármacos , Nanopartículas/química , Ratas , Masculino , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Dolor de la Región Lumbar/tratamiento farmacológico , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Sirolimus/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Núcleo Pulposo/metabolismo , Inflamación/tratamiento farmacológico , Citocinas/metabolismo , Biomimética/métodos , Modelos Animales de Enfermedad , Factor de Crecimiento Nervioso/metabolismo , Células RAW 264.7RESUMEN
A patient had multiple erythematous macules and patches on the trunk, hyperpigmented patches on the intergluteal cleft and subgluteal fold, and poikiloderma in the axillae; results of laboratory testing, including antinuclear antibody test, were unremarkable. What is the diagnosis and what would you do next?
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BACKGROUND: Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis-gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome. RESULTS: The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts. CONCLUSION: These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association. HIGHLIGHTS: 1 Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. 2 Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. 3 Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients.
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Síndrome Coronario Agudo , Microplásticos , Humanos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/inducido químicamente , Masculino , Persona de Mediana Edad , Femenino , Microplásticos/toxicidad , Estudios Transversales , Anciano , Factores de Riesgo , Estudios de Casos y Controles , Aterosclerosis/sangre , Aterosclerosis/inducido químicamente , Biomarcadores/sangre , AdultoRESUMEN
Gut microbiota of centenarians has garnered significant attention in recent years, with most studies concentrating on the analysis of microbial composition. However, there is still limited knowledge regarding the consistent signatures of specific species and their biological functions, as well as the potential causal relationship between gut microbiota and longevity. To address this, we performed the fecal metagenomic analysis of eight longevous populations at the species and functional level, and employed the Mendelian randomization (MR) analysis to infer the causal associations between microbial taxa and longevity-related traits. We observed that several species including Eisenbergiella tayi, Methanobrevibacter smithii, Hungatella hathewayi, and Desulfovibrio fairfieldensis were consistently enriched in the gut microbiota of long-lived individuals compared to younger elderly and young adults across multiple cohorts. Analysis of microbial pathways and enzymes indicated that E. tayi plays a role in the protein N-glycosylation, while M. smithii is involved in the 3-dehydroquinate and chorismate biosynthesis. Furthermore, H. hathewayi makes a distinct contribution to the purine nucleobase degradation I pathway, potentially assisting the elderly in maintaining purine homeostasis. D. fairfieldensis contributes to the menaquinone (vitamin K2) biosynthesis, which may help prevent age-related diseases such as osteoporosis-induced fractures. According to MR results, Hungatella was significantly positively correlated with parental longevity, and Desulfovibrio also exhibited positive associations with lifespan and multiple traits related to parental longevity. Additionally, Alistipes and Akkermansia muciniphila were consistently enriched in the gut microbiota of the three largest cohorts of long-lived individuals, and MR analysis also suggests their potential causal relationships with longevity. Our findings reveal longevity-associated gut microbial signatures, which are informative for understanding the role of microbiota in regulating longevity and aging.
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Bacterias , Heces , Microbioma Gastrointestinal , Longevidad , Humanos , Anciano de 80 o más Años , Heces/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Femenino , Adulto , Masculino , Anciano , Adulto Joven , Metagenómica , Persona de Mediana Edad , Desulfovibrio/genética , Desulfovibrio/metabolismoRESUMEN
Objective: Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China. Methods: In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5. Results: Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV. Conclusion: G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China.