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1.
J Am Chem Soc ; 146(20): 13797-13804, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38722223

RESUMEN

Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as ∼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.

2.
Sci Total Environ ; 932: 173067, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38723964

RESUMEN

Optimizing N application under straw-covered strip tillage is of great significance to the rational utilization of stover resources as well as ensure food and ecosystem security, and especially N2O emissions from agricultural systems. Quantifying N2O emissions and even the carbon footprint (CF) from agricultural systems is crucial for future protecting agricultural production systems. A two-year field experiment was conducted on black soil in Northeast China, which set up two tillage systems: strip tillage with straw returning (ST) and conventional tillage (control: CT) without straw and three nitrogen rates: 0, farmers' practice (Nfp 240 kg hm-2), and optimized nitrogen fertilizer (Nopt 180 kg hm-2). We examined the characteristics of N2O emissions and CF under the ST and CT systems. Among them, we indirectly calculated GHG emissions using the LCA method. Compared with CT, the ST system significantly reduces indirect GHG emissions, but did significantly increase direct cumulative N2O emissions by 20.7 %, most likely because the higher soil residual nitrate nitrogen content, WFPS, and soil temperature under ST was 13.0 %, 2 % and 5.7 % higher than that under CT. Nopt treatment markedly reduced cumulative N2O emissions by 36.0 %, CFarea, CFyield, and CFNPV by 22.4 %, 23.1 %, and 23.5 % in ST, respectively, compared to Nfp. The reduction in energy use of machinery in ST results in lower fuel consumption and thus generating less CF. What's more, the decrease of CFyield and CFNPV between nitrogen application treatments under ST was 5.2 % and 7.7 % higher than CT, respectively. ST system can effectively achieve higher grain yield and mitigate GHG emissions on black soil in Northeast China compared with CT, but attention should be paid to N2O emissions in the soil during the maize growth period. The sustainability of balancing GHG emissions, and economic and environmental benefits can be achieved by optimizing nitrogen fertilizer manage.

3.
Chemosphere ; 357: 141954, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615964

RESUMEN

Aerobic denitrification has emerged as a promising and efficient method for nitrogen removal from wastewater. However, the direct application of aerobic denitrifying bacteria has faced challenges such as low nitrogen removal efficiency, bacterial loss, and poor stability. To address these issues, this study developed a novel microbial particle carrier using NaHCO3-modified polyvinyl alcohol (PVA)/sodium alginate (SA) gel (NaHCO3-PVA/SA). This carrier exhibits several advantageous properties, including excellent mass transfer efficiency, favorable biocompatibility, convenient film formation, abundant biomass, and exceptional pollutant treatment capacity. The carrier was modified with 0.3% NaHCO3, 8.0% PVA, and 1.0% SA, resulting in a remarkable 3.4-fold increase in the average pore diameter and a 12.8% improvement in mass transfer efficiency. This carrier was utilized to immobilize the aerobic denitrifying bacterium Stutzerimonas stutzeri W-2 to enhance nitrogen removal (NaHCO3-PVA/SA@W-2), resulting in a NO3--N removal efficiency of 99.06%, which was 21.39% higher than that without modification. Compared with the non-immobilized W-2, the degradation efficiency was improved by 43.70%. After five reuses, the NO3--N and TN removal rates remained at 99% and 93.01%, respectively. These results provide a solid foundation for the industrial application of the modified carrier as an effective tool for nitrogen removal in large-scale wastewater treatment processes.


Asunto(s)
Alginatos , Desnitrificación , Nitrógeno , Alcohol Polivinílico , Aguas Residuales , Alcohol Polivinílico/química , Alginatos/química , Nitrógeno/metabolismo , Aguas Residuales/química , Aguas Residuales/microbiología , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/metabolismo , Aerobiosis , Pseudomonas stutzeri/metabolismo , Biodegradación Ambiental , Células Inmovilizadas/metabolismo
4.
Biotechnol Adv ; 72: 108348, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38531490

RESUMEN

The rapid development of synthetic biology has significantly improved the capabilities of mono-culture systems in converting different substrates into various value-added bio-chemicals through metabolic engineering. However, overexpression of biosynthetic pathways in recombinant strains can impose a heavy metabolic burden on the host, resulting in imbalanced energy distribution and negatively affecting both cell growth and biosynthesis capacity. Synthetic consortia, consisting of two or more microbial species or strains with complementary functions, have emerged as a promising and efficient platform to alleviate the metabolic burden and increase product yield. However, research on synthetic consortia is still in its infancy, with numerous challenges regarding the design and construction of stable synthetic consortia. This review provides a comprehensive comparison of the advantages and disadvantages of mono-culture systems and synthetic consortia. Key considerations for engineering synthetic consortia based on recent advances are summarized, and simulation and computational tools for guiding the advancement of synthetic consortia are discussed. Moreover, further development of more efficient and cost-effective synthetic consortia with emerging technologies such as artificial intelligence and machine learning is highlighted.


Asunto(s)
Inteligencia Artificial , Consorcios Microbianos , Vías Biosintéticas , Ingeniería Metabólica/métodos , Biología Sintética/métodos
5.
Anal Chim Acta ; 1298: 342411, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38462335

RESUMEN

Early detection of cancer has a profound impact on patient survival and treatment outcomes considering high treatment success rates and reduced treatment complexity. Here, we developed a portable photoelectrochemical (PEC) immune platform for sensitive testing of alpha-fetoprotein (AFP) based on Pt nanocluster (Pt NCs) loaded defective-state g-C3N4 photon-electron transducers. The broad forbidden band structure of g-C3N4 was optimized by the nitrogen doping strategy and additional homogeneous porous structure was introduced to further enhance the photon utilization. In addition, the in-situ growth of Pt NCs provided efficient electron transfer catalytic sites for sacrificial agents, which were used to further improve the sensitivity of the sensor. Efficient photoelectric conversion under a hand-held flashlight was determined by the geometry of the transducer and the energy band design, and the portable design of the PEC sensor was realized. The developed sensing platform exhibited a wide linear response range (0.1-50 ng mL-1) and low limit of detection (0.043 ng mL-1) for AFP under optimum conditions. This work provides a new idea for designing portable PEC biosensing platforms to meet the current mainstream POC testing needs.


Asunto(s)
Técnicas Biosensibles , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Técnicas Electroquímicas , Límite de Detección , Inmunoensayo
6.
Adv Sci (Weinh) ; 11(15): e2304879, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38342632

RESUMEN

In the current prevalent complex electromagnetic (EM) environment, intelligent methods for versatile and integrated control of EM waves using compact devices are both essential and challenging. These varied wave control objectives can at times conflict with one another, such as the need for broad absorption to remain inconspicuous, while also requiring enhanced backward scattering for highly reliable tracing and secure communication. To address these sophisticated challenges, a microwave-frequency reconfigurable tri-mode metasurface (RTMM) is introduced. The proposed innovation enables three distinct operational modes: broadband low observation, enhanced EM wave tracing, and backscatter communication over a wide-angle range by simple control of the PIN diodes embedded in each meta-atom. The proof-of-concept demonstration of the fabricated prototype verified the switchable tri-mode performance of the RTMM. This proposed RTMM can be adapted to various applications, including EM shielding, target detection, and secure communication in complex and threatening EM environments, paving the way for environmentally-adaptive EM wave manipulation.

7.
J Psychiatr Res ; 172: 47-51, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38359617

RESUMEN

Depressive symptoms is a public health concern worldwide, and adolescents may experience more depressive symptoms. Although the relationship between borderline personality features (BPFs) disorder and depressive symptoms has been established, it is unclear whether the longitudinal relationship between them is unidirectional or bidirectional and whether these symptoms are different between boys and girls. In this study, Chinese adolescents (1608 total and separately 972 for boys and 636 girls) were enrolled between September 2019 and September 2021, and we analyzed the data using a cross-lagged model. The results suggested a bidirectional relationship between BPFs and depressive symptoms in boys (ß = 0.191 and 0.117, P < 0.001). However, in girls, depressive symptoms were predicted based on BPFs (ß = 0.225, P < 0.001), whereas BPFs were not predicted based on depressive symptoms (ß = 0.035, P = 0.535). The findings suggest that borderline personality traits and depressive symptoms are only bilaterally associated in girls, which also provides important evidence for the treatment and prevention of adolescent BPFs and depressive symptoms.


Asunto(s)
Trastorno de Personalidad Limítrofe , Depresión , Masculino , Femenino , Humanos , Adolescente , Depresión/epidemiología , Depresión/diagnóstico , Estudios de Cohortes , Trastorno de Personalidad Limítrofe/epidemiología , Trastorno de Personalidad Limítrofe/diagnóstico , Personalidad , Estudios Longitudinales
8.
Phys Rev Lett ; 132(6): 065106, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38394567

RESUMEN

Understanding the self-organization of the most promising internal transport barrier in fusion plasmas needs a long-time nonlinear gyrokinetic global simulation. The neighboring equilibrium update method is proposed, which solves the secularity problem in a perturbative simulation and speeds up the numerical computation by more than 10 times. It is found that the internal transport barrier emerges at the magnetic axis due to inward propagated turbulence avalanche, and its outward expansion is the catastrophe of self-organized structure induced by outward propagated avalanche.

9.
Eur J Pharmacol ; 967: 176376, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38336014

RESUMEN

Renal tubular injury is a critical factor during the early stages of diabetic nephropathy (DN). Proximal tubular epithelial cells, which contain abundant mitochondria essential for intracellular homeostasis, are susceptible to disruptions in the intracellular environment, making them especially vulnerable to diabetic state disorders, which may be attributed to their elevated energy requirements and reliance on aerobic metabolism. It is widely thought that overactivation of the polyol pathway is implicated in DN pathogenesis, and inhibition of aldose reductase (AR), the rate-limiting enzyme in this pathway, represents a promising therapeutic avenue. WJ-39, a novel aldose reductase inhibitor, was investigated in this study for its protective effects on renal tubules in DN and the underlying mechanisms. Our findings revealed that WJ-39 significantly ameliorated the renal tubular morphology in high-fat diet (HFD)/streptozotocin (STZ)-induced DN rats, concurrently inhibiting fibrosis. Notably, WJ-39 safeguarded the structure and function of renal tubular mitochondria by enhancing mitochondrial dynamics. This involved the regulation of mitochondrial fission and fusion proteins and the promotion of PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. Furthermore, WJ-39 demonstrated the inhibition of endogenous apoptosis by mitigating the production of mitochondrial reactive oxygen species (ROS). The protective effects of WJ-39 on mitochondria and apoptosis were countered in high glucose-treated HK-2 cells upon transfection with PINK1 siRNA. Overall, our findings suggest that WJ-39 protects the structural and functional integrity of renal tubules in DN, which may be attributed to its capacity to inhibit aldose reductase activity, activate the PINK1/Parkin signaling pathway, promote mitophagy, and alleviate apoptosis.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Ratas , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Aldehído Reductasa/metabolismo , Proteínas Quinasas/metabolismo , Transducción de Señal , Inhibidores Enzimáticos/farmacología , Ubiquitina-Proteína Ligasas/metabolismo
10.
Am J Sports Med ; 52(2): 474-484, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38197156

RESUMEN

BACKGROUND: Knowledge of acromioclavicular (AC) joint kinematics and distance may provide insight into the biomechanical function and development of new treatment methods. However, accurate data on in vivo AC kinematics and distance between the clavicle and acromion remain unknown. PURPOSE/HYPOTHESIS: The purpose of this study was to investigate 3-dimensional AC kinematics and distance during arm elevation in abduction, scaption, and forward flexion in a healthy population. It was hypothesized that AC kinematics and distance would vary with the elevation angle and plane of the arm. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 19 shoulders of healthy participants were enrolled. AC kinematics and distance were investigated with a combined dual fluoroscopic imaging system and computed tomography. Rotation and translation of the AC joint were calculated. The AC distance was measured as the minimum distance between the medial border of the acromion and the articular surface of the distal clavicle (ASDC). The minimum distance point (MDP) ratio was defined as the length between the MDP and the posterior edge of the ASDC divided by the anterior-posterior length of the ASDC. AC kinematics and distance between different elevation planes and angles were compared. RESULTS: Progressive internal rotation, upward rotation, and posterior tilt of the AC joint were observed in all elevation planes. The scapula rotated more upward relative to the clavicle in abduction than in scaption (P = .002) and flexion (P = .005). The arm elevation angle significantly affected translation of the AC joint. The acromion translated more laterally and more posteriorly in scaption than in abduction (P < .001). The AC distance decreased from the initial position to 75° in all planes and was significantly greater in flexion (P < .001). The MDP ratio significantly increased with the elevation angle (P < .001). CONCLUSION: Progressive rotation and significant translation of the AC joint were observed in different elevation planes. The AC distance decreased with the elevation angle from the initial position to 75°. The minimum distance between the ASDC and the medial border of the acromion moved anteriorly as the shoulder elevation angle increased. CLINICAL RELEVANCE: These results could serve as benchmark data for future studies aiming to improve the surgical treatment of AC joint abnormalities to restore optimal function.


Asunto(s)
Articulación Acromioclavicular , Articulación del Hombro , Humanos , Fenómenos Biomecánicos , Imagenología Tridimensional , Húmero , Escápula , Acromion/diagnóstico por imagen , Articulación Acromioclavicular/diagnóstico por imagen , Articulación Acromioclavicular/cirugía , Rango del Movimiento Articular
11.
Nat Commun ; 15(1): 518, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38225235

RESUMEN

The construction of N-N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N-N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC (N-heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize structurally diverse N-N axially chiral pyrroles and indoles with vicinal central chirality or bearing a 2,3-dihydropyrimidin-4-one moiety in moderate to good yields and excellent enantioselectivities. Further synthetic transformations of the obtained axially chiral pyrroles and indoles derivative products are demonstrated. The reaction mechanism and the origin of enantioselectivity are understood through DFT calculations.

12.
Org Lett ; 26(3): 702-707, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38206074

RESUMEN

We report herein an efficient NHC-catalyzed kinetic resolution of acyclic tertiary propargylic alcohols that provides them in high to excellent enantioselectivity. This is the first example of kinetic resolution realized by enantioselective acylation. The recovered enantioenriched alcohols can be facilely converted into other valuable compounds such as densely functionalized tertiary alcohols and carbmates in high yields and excellent stereopurity. Density functional theory calculations were performed to determine the reaction mechanism and to understand the origin of enantiodiscrimination.

13.
Talanta ; 271: 125679, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38245958

RESUMEN

The development of efficient, rapid, portable, and accurate analysis of veterinary drug residues in food matrices is in great demand for food safety assessment. Here, we have developed a smartphone-integrated platform for fluorometric quantification of metronidazole (MNZ) residues and constructed a sensor array for discrimination of different nitroimidazole antibiotics (NIIMs). Multicolor CDs (B-CDs, C-CDs, Y-CDs, and R-CD) were prepared and showed different fluorescence response to MNZ. The fluorescence of C-CDs was quenched Because of the inner filter effect (IFE) between the C-CDs and MNZ, while that of R-CDs was enhanced due to the passivation of surface defects by MNZ. Based on the response pattern, the fluorometric quantification of MNZ based on the fluorescence images of C-CD + R-CD system (R/G values) was achieved with a low detection limit of 0.45 µM. By designing a smartphone-integrated platform, the analysis can be completed within 20 min. In addition, a fluorescence sensor array based C-CDs and R-CDs was also developed. The unique fingerprint of each NIIMs was obtained by linear discriminant analysis (LDA) of the response patterns, indicating an effective discrimination of five NIIMs. Moreover, the platform was used for quantification of MNZ in food samples and the recoveries were within 84.0-106.3 % with relative standard deviations 1.2-10.2 %. Therefore, the proposed method shows great potential as a universal platform for rapid detection of veterinary drug residues.


Asunto(s)
Nitroimidazoles , Puntos Cuánticos , Drogas Veterinarias , Antibacterianos , Carbono , Fluorometría , Colorantes Fluorescentes , Espectrometría de Fluorescencia
14.
Adv Sci (Weinh) ; 11(9): e2306662, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38093511

RESUMEN

Synthetic consortia have emerged as a promising biosynthetic platform that offers new opportunities for biosynthesis. Genome-scale metabolic network models (GEMs) with complex constraints are extensively utilized to guide the synthesis in monocultures. However, few methods are currently available to guide the rational construction of synthetic consortia for predicting the optimal allocation strategy of synthetic pathways aimed at enhancing product synthesis. A standardized method to construct the co-cultivated Enzyme Constraint metabolic network model (CulECpy) is proposed, which integrates enzyme constraints and modular interaction scale constraints based on the research concept of "independent + global". This method is applied to construct several synthetic consortia models, which encompassed different target products, strains, synthetic pathways, and compositional structures. Analyzing the model, the optimal pathway allocation and initial inoculum ratio that enhance the synthesis of target products by synthetic consortia are predicted and verified. When comparing with the constructed co-culture synthesis system, the normalized root mean square error of all optimal theoretical yield simulations is found to be less than or equal to 0.25. The analyses and verifications demonstrate that the method CulECpy can guide the rational construction of synthetic consortia systems to facilitate biochemical synthesis.


Asunto(s)
Redes y Vías Metabólicas , Consorcios Microbianos
15.
Epidemiol Psychiatr Sci ; 32: e52, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37553982

RESUMEN

AIMS: Previous cross-sectional and case-control studies have proposed that decreased vitamin D levels are positively correlated with the risk of suicidality in adults. However, limited studies have examined the association between vitamin D and suicidality in adolescents. This study aimed to investigate the relationship between serum vitamin D and suicidality risk among early adolescents. METHODS: Data were obtained from a Chinese early adolescent cohort. In this cohort, seventh-grade students from a middle school in Anhui Province were invited to voluntarily participate in the baseline assessments and provide peripheral blood samples (in September 2019). The participants were followed up annually (in September 2020 and September 2021). Serum 25-hydroxyvitamin D [25(OH)D] and vitamin D-related single-nucleotide polymorphisms at baseline were measured in November 2021. Traditional observational and Mendelian randomization (MR) analyses were performed to examine the relationship between serum 25(OH)D at baseline and the risk of baseline and incident suicidality (i.e., suicidal ideation [SI], plans and attempts). RESULTS: Traditional observational analysis did not reveal a significant linear or non-linear association of serum 25(OH)D concentration with the risks of baseline and 2-year incident suicidality in the total sample (P > .05 for all). Sex-stratified analysis revealed a non-linear association between the 25(OH)D concentration and the risk of baseline SI in women (Poverall = .002; Pnon-linear = .001). Moreover, the risk of baseline SI in the 25(OH) insufficiency group was lower than that in the 25(OH) deficiency group in the total sample (odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.51-0.92, P = .012). This difference remained significant in women (OR = 0.59, 95% CI = 0.40-0.87, P = .008) but not in men (OR = 0.78, 95% CI = 0.53-1.15, P = .205). Additionally, both linear and non-linear MR analyses did not support the causal effect of serum 25(OH)D concentration on the risk of baseline, 1-year and 2-year incident suicidality (P > .05 for all). CONCLUSIONS: This study could not confirm the causal effect of vitamin D on suicidality risk among Chinese early adolescents. Future studies must confirm these findings with a large sample size.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Suicidio , Adolescente , Femenino , Humanos , Masculino , Estudios Transversales , Pueblos del Este de Asia , Ideación Suicida , Vitamina D
16.
J Affect Disord ; 340: 462-470, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37573894

RESUMEN

BACKGROUND: Child maltreatment may lead to sleep disturbance during the critical period of child development. Our study examined the effect of maltreatment in early childhood on trajectories of sleep quality among early adolescents. METHODS: The study included 1611 participants (mean ± standard deviation age at baseline: 12.5 ± 0.5 years) from a middle school in southeastern China. Of these participants, 60.5 % were males. Information on early childhood maltreatment during pre-seventh grade was obtained through a self-report questionnaire at baseline, and sleep quality was collected at baseline and during follow-up. We used a group-based trajectory model to characterize trajectories of sleep quality. RESULTS: The study identified four trajectories of sleep quality, namely the low sleep score group (25.0 %), the moderate-low sleep score group (51.0 %), the moderate-increasing sleep score (17.0 %), and the high-decreasing sleep score (7.0 %) group. After adjusting for covariates, the findings revealed that emotional abuse and physical abuse were associated with an increased risk of developing new-onset sleep disturbances in early adolescents. Particularly, emotional abuse (incidence rate ratio = 1.71, 95 % confidence interval: 1.08-2.71) significantly increased the risk of belonging to the high-decreasing sleep score group. Moreover, there existed a dose-response relationship between early childhood maltreatment and sleep quality trajectories, with a higher number of maltreatment types in early childhood correlating with a greater risk of belonging to the high-decreasing sleep score group. CONCLUSIONS: The findings of our study provide compelling evidence indicating that specific types and cumulative maltreatment during early childhood contribute to sleep disturbances among early adolescents. The study findings highlight the significance of preventing and reducing early childhood maltreatment to enhance sleep quality during early adolescence.


Asunto(s)
Maltrato a los Niños , Calidad del Sueño , Masculino , Niño , Humanos , Preescolar , Adolescente , Femenino , Pueblos del Este de Asia , Maltrato a los Niños/psicología , Encuestas y Cuestionarios , Abuso Físico
17.
Eur J Med Chem ; 257: 115532, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37295161

RESUMEN

In combination with allopurinol, tranilast is used as an urate transporter 1 (URAT1) inhibitor for the treatment of hyperuricemia, but its structure-activity relationship concerning URAT1 inhibitory activity is rarely studied. In this paper, analogs 1-30 were designed and synthesized using scaffold hopping strategy on the basis of tranilast and the privileged scaffold indole. Then, URAT1 activity was evaluated using 14C-uric acid uptake assay with HEK293-URAT1 overexpressing cells. Compared with tranilast (inhibitory rate = 44.9% at 10 µM), most compounds displayed apparent inhibitory effects, ranging from 40.0% to 81.0% at 10 µM on URAT1. Surprisingly, along with the bringing in of a cyano group at the 5-position of indole ring, compounds 26 and 28-30 exerted xanthine oxidase (XO) inhibitory activity. In particular, compound 29 presented potency on URAT1 (48.0% at 10 µM) and XO (IC50 = 1.01 µM). Molecular simulation analysis revealed that the basic structure of compound 29 had an affinity with URAT1, and XO. Furthermore, compound 29 demonstrated a significant hypouricemic effect in a potassium oxonate-induced hyperuricemia rat model at an oral dose of 10 mg/kg during in vivo tests. In summary, tranilast analog 29 was identified as a potent dual-target inhibitor of URAT1 and XO, and a promising lead compound for further investigation.


Asunto(s)
Hiperuricemia , Xantina Oxidasa , Animales , Humanos , Ratas , Ácidos Carboxílicos/farmacología , Células HEK293 , Hiperuricemia/inducido químicamente , Hiperuricemia/tratamiento farmacológico , Indoles/uso terapéutico , Tiazoles/uso terapéutico
18.
Nat Med ; 29(6): 1476-1486, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37291211

RESUMEN

Alcohol consumption accounts for ~3 million annual deaths worldwide, but uncertainty persists about its relationships with many diseases. We investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of >512,000 adults (41% men), including 168,050 genotyped for ALDH2- rs671 and ADH1B- rs1229984 , with >1.1 million ICD-10 coded hospitalized events. At baseline, 33% of men drank alcohol regularly. Among men, alcohol intake was positively associated with 61 diseases, including 33 not defined by the World Health Organization as alcohol-related, such as cataract (n = 2,028; hazard ratio 1.21; 95% confidence interval 1.09-1.33, per 280 g per week) and gout (n = 402; 1.57, 1.33-1.86). Genotype-predicted mean alcohol intake was positively associated with established (n = 28,564; 1.14, 1.09-1.20) and new alcohol-associated (n = 16,138; 1.06, 1.01-1.12) diseases, and with specific diseases such as liver cirrhosis (n = 499; 2.30, 1.58-3.35), stroke (n = 12,176; 1.38, 1.27-1.49) and gout (n = 338; 2.33, 1.49-3.62), but not ischemic heart disease (n = 8,408; 1.04, 0.94-1.14). Among women, 2% drank alcohol resulting in low power to assess associations of self-reported alcohol intake with disease risks, but genetic findings in women suggested the excess male risks were not due to pleiotropic genotypic effects. Among Chinese men, alcohol consumption increased multiple disease risks, highlighting the need to strengthen preventive measures to reduce alcohol intake.


Asunto(s)
Consumo de Bebidas Alcohólicas , Pueblos del Este de Asia , Gota , Adulto , Femenino , Humanos , Masculino , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/etnología , Consumo de Bebidas Alcohólicas/genética , Aldehído Deshidrogenasa Mitocondrial/genética , Pueblos del Este de Asia/estadística & datos numéricos , Etanol , Genotipo , Factores de Riesgo , Enfermedad/etnología , Enfermedad/etiología , Enfermedad/genética , China/epidemiología
19.
Bioresour Technol ; 385: 129394, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37369317

RESUMEN

Aerobic granular sludge (AGS) has proved to be a promising biotechnology for microplastics wastewater treatment. However, polyacrylonitrile microplastics (PAN MPs), the most widely used plastic in textile materials, have not been investigated. Therefore, the effect of the neglected PAN MPs on AGS at different concentrations (1, 10, and 100 mg/L) was evaluated. The results indicated that PAN MPs with 1 and 10 mg/L concentrations had no obvious effect on granular stability and nutrient removal performance, but greatly promoted the secretion of EPS. Remarkably, the granule structure was severely damaged under 100 mg/L PAN MPs. Moreover, microbial community analysis showed that phylum Proteobacteria played a dominant role in resistance to PAN MPs. Metabolic analysis further revealed that genes related to denitrification pathway (nasA, nirK, nirS and norB) and membrane transport were significantly inhibited under PAN MPs stress. This study may provide additional information on the treatment of microplastics wastewater using AGS.


Asunto(s)
Microbiota , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Microplásticos , Plásticos , Eliminación de Residuos Líquidos , Reactores Biológicos , Aerobiosis , Nitrógeno
20.
J Affect Disord ; 334: 197-204, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37150219

RESUMEN

BACKGROUND: Several cross-sectional studies have suggested a strongly positive link between sleep and aggressive behaviour; however, longitudinal studies reporting the relationship between sleep and aggressive behaviour are lacking. This study aimed to examine whether a bidirectional relationship exists between sleep quality or duration and aggressive behaviour in early adolescents. METHODS: A total of 1579 early adolescents (60.9 % boys) from the Chinese Early Adolescents Cohort study were included in this study. Data on sleep quality, sleep duration and aggressive behaviour collected at two time points (September 2019 and September 2021) were used, and the bidirectional relationship between sleep quality or duration and aggressive behaviour was examined using a cross-lagged model. RESULTS: The results revealed a bidirectional relationship between low sleep quality and highly aggressive behaviour. A shorter sleep duration did not predict highly aggressive behaviour, whereas only highly aggressive behaviour predicted a shorter sleep duration. CONCLUSIONS: Sleep quality and aggressive behaviour were interrelated over time among adolescents. However, sleep duration did not predict aggressive behaviour, suggesting that sleep quality, instead of sleep duration, should be the primary target for managing aggressive behaviour.


Asunto(s)
Agresión , Duración del Sueño , Calidad del Sueño , Humanos , Masculino , Femenino , Niño , Adolescente , Agresión/fisiología , Agresión/psicología , Estudios Longitudinales
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