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1.
Front Cell Infect Microbiol ; 14: 1327083, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562964

RESUMO

Background: Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases. Methods: Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates. Results: The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10-3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10-3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10-2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10-2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10-3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity. Conclusion: This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.


Assuntos
Acne Vulgar , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Bacteroides/genética
2.
Adv Mater ; : e2404672, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634272

RESUMO

The performance of single-atom catalysts is greatly influenced by the chemical environment surrounding the central atom. In this study, a salt-assisted method was employed to transform the tetrahedral coordination structure of ZIF-8 into a planar square coordination structure without altering the ligands. During the subsequent carbonization process, concurrent with the evaporation of zinc atoms, the structure of the nitrogen and carbon carriers (NC carriers) undergo a transition from five-membered rings to six-membered rings to preserve the 2D structure. Following carbonization, the 2d-NC carrier predominantly comprises pyridine N within six-membered rings, whereas the 3d-NC carrier contains a higher proportion of pyrrole N within five-membered rings, along with graphite N that unavailable for coordination sites. This transition result in the generation of additional defect sites on the 2d-NC substrates. Hence, the Pt single-atom catalysts with planar square coordination symmetries can be precisely prepared via electrodeposition (denoted as 2d-Pt SAC). By utilizing the structural characteristics of the 2d-NC carrier, it is beneficial to construct Pt SAs with higher density than that on 3d-NC. The Pt loading of 2d-Pt SAC is 0.49 ± 0.03 µg cm-2, higher than that of 3d-Pt SAC (0.37 ± 0.04 µg cm-2). In the context of the hydrogen oxidation reaction (HOR) electrocatalysis, these single atom catalysts with 2d coordination exhibited exchange current densities of 1.47 mA cm-2. Moreover, under an overpotential of 50 mV, it achieved mass activities of 2396 A gPt -1 (32 times higher than commercial Pt/C catalyst, 2 times higher than 3d-PtNC). Our findings elucidate the influence of coordination symmetry on the performance of single-atom catalysts, offering a novel synthetic approach that may have implications for future industrial synthesis endeavors. This article is protected by copyright. All rights reserved.

3.
Nat Commun ; 15(1): 3416, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649713

RESUMO

In-depth comprehension and modulation of the electronic structure of the active metal sites is crucial to enhance their intrinsic activity of electrocatalytic oxygen evolution reaction (OER) toward anion exchange membrane water electrolyzers (AEMWEs). Here, we elaborate a series of amorphous metal oxide catalysts (FeCrOx, CoCrOx and NiCrOx) with high performance AEMWEs by high-valent chromium dopant. We discover that the positive effect of the transition from low to high valence of the Co site on the adsorption energy of the intermediate and the lower oxidation barrier is the key factor for its increased activity by synchrotron radiation in-situ techniques. Particularly, the CoCrOx anode catalyst achieves the high current density of 1.5 A cm-2 at 2.1 V and maintains for over 120 h with attenuation less than 4.9 mV h-1 in AEMWE testing. Such exceptional performance demonstrates a promising prospect for industrial application and providing general guidelines for the design of high-efficiency AEMWEs systems.

4.
J AOAC Int ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492563

RESUMO

BACKGROUND: Arcae concha and Meretricis concha cyclinae concha are two marine shellfish herbs with similar composition and efficacy, which are usually calcined and used clinically. OBJECTIVE: This study investigated variations in the inorganic and organic components of Arcae concha and Meretricis concha cyclinae concha from different production regions, both Arcae concha and Meretricis concha cyclinae concha. The aim was to enhance the understanding of these two types of marine shell traditional Chinese medicine (msTCM) and provide a foundation for their future development and application. METHOD: Spectroscopic techniques, including infrared spectroscopy, X-ray spectroscopy, and X-ray fluorescence spectroscopy, were used to analyze the calcium carbonate (CaCO3) crystal and trace elements. Thermogravimetric analysis was used to investigate the decomposition process during heating. The proteins were quantified using the BCA protein assay kit. Principal component analysis (PCA) was used to classify inorganic elements in the two marine shellfish traditional Chinese medicines. RESULTS: No significant differences among the various production regions. The crystal structure of CaCO3 in the raw products was aragonite, but it transformed into calcite after calcination. The contents of Ca, Na, Sr, and other inorganic elements were highest. The protein content was significantly reduced after calcination. Therefore, these factors cannot accurately reflect the internal quality of TCM, rendering qualitative identification challenging. CaCO3 dissolution in the decoction of Arcae concha and Meretricis concha cyclinae concha increased after calcination, aligning with the clinical application of calcined shell TCM. PCA revealed the inorganic elements in them, indicating that the variation in trace element composition among different drugs leads to differences in their therapeutic focus, which should be considered during usage. CONCLUSION: This study clarified the composition and structure changes of corrugated and clam shell before and after calcining, and laid the foundation for the comprehensive utilization of Marine traditional Chinese medicine. HIGHLIGHTS: These technical representations reveal the differences between raw materials and processed products, which will provide support for the quality control of other shellfish TCMS.

5.
Lipids Health Dis ; 23(1): 81, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509584

RESUMO

BACKGROUND: Obesity is associated with extensive white adipose tissue (WAT) expansion and remodeling. Healthy WAT expansion contributes to the maintenance of energy balance in the liver, thereby ameliorating obesity-related hepatic steatosis. Tissue-resident mesenchymal stromal cell populations, including PDGFRß + perivascular cells, are increasingly recognized pivotal as determinants of the manner in which WAT expands. However, the full array of regulatory factors controlling WAT stromal cell functions remains to be fully elucidated. Hypoxia-inducible factors (HIFs) are critical regulators in WAT stromal cell populations such as adipocyte precursor cells (APCs). It is revealed that HIF1α activation within PDGFRß + stromal cells results in the suppression of de novo adipogenesis and the promotion of a pro-fibrogenic cellular program in obese animals. However, the role of HIF2α in PDGFRß + cells remains undetermined in vivo. METHODS: New genetic models were employed in which HIF1α (encoded by the Hif1a gene) and HIF2α (encoded by the Epas1 gene) are selectively inactivated in PDGFRß + cells in an inducible manner using tamoxifen (TAM). With these models, both in vitro and in vivo functional analysis of PDGFRß + cells lacking HIF proteins were performed. Additionally, comprehensive metabolic phenotyping in diet-induced mouse models were performed to investigate the roles of PDGFRß + cell HIF proteins in WAT remodeling, liver energy balance and systemic metabolism. RESULTS: Unlike HIF1α inactivation, the new findings in this study suggest that inducible ablation of HIF2α in PDGFRß + cells does not cause apparent effects on WAT expansion induced by obesogenic diet. The adipogenic ability of PDGFRß + APCs is not significantly altered by genetic HIF2α ablation. Moreover, no difference of key parameters associated with healthy WAT remodeling such as improvements of WAT insulin sensitivity, reduction in metabolic inflammation, as well as changes in liver fat accumulation or systemic glucose metabolism, is detected in PDGFRß + cell Epas1-deficient mice. CONCLUSION: The new findings in this study support that, in contrast to HIF1α, PDGFRß + cell HIF2α appears dispensable for WAT metabolic remodeling and the resulting effects on liver metabolic homeostasis in diet-induced obesity, underscoring the isoform-specific roles of HIFα proteins in the regulation of adipose tissue biology.


Assuntos
Tecido Adiposo Branco , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Obesidade , Animais , Camundongos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
7.
J Hum Genet ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429412

RESUMO

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P < 4.8 × 10-5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.

8.
Nano Lett ; 24(10): 3213-3220, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426819

RESUMO

Rational design of well-defined active sites is crucial for promoting sluggish oxygen reduction reactions. Herein, leveraging the surfactant-oriented and solvent-ligand effects, we develop a facile self-assembly strategy to construct a core-shell catalyst comprising a high-index Pt shell encapsulating a PtCu3 intermetallic core with efficient oxygen-reduction performance. Without undergoing a high-temperature route, the ordered PtCu3 is directly fabricated through the accelerated reduction of Cu2+, followed by the deposition of the remaining Pt precursor onto its surface, forming high-index steps oriented by the steric hindrance of surfactant. This approach results in a high half-wave potential of 0.911 V versus reversible hydrogen electrode, with negligible deactivation even after 15000-cycle operation. Operando spectroscopies identify that this core-shell catalyst facilitates the conversion of oxygen-involving intermediates and ensures antidissolution ability. Theoretical investigations rationalize that this improvement is attributed to reinforced electronic interactions around high-index Pt, stabilizing the binding strength of rate-determining OHads species.

9.
J Phys Chem Lett ; 15(11): 3071-3077, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38466813

RESUMO

The comprehensive understanding toward the dealloying process is crucial for designing alloy catalysts employed in the oxygen reduction reaction (ORR). However, the specific leaching procedure and subsequent reconstruction of the dealloyed catalyst still remain unclear. Herein, we employ in situ X-ray absorption fine structure spectroscopy to monitor the dealloying process of a two-dimensional PtTe ordered alloy, known for its enhanced ORR activity. Our findings reveal the unsynchronous evolutions of Pt and Te sites, wherein the Pt component undergoes a structural transformation prior to the complete leaching of Te, leading to the formation of a defect-rich Pt catalyst. This dealloyed catalyst exhibits a significant enhancement in ORR activity, featuring a half-wave potential of 0.90 V versus the reversible hydrogen electrode and a mass activity of 0.62 A mgPt-1, outperforming the performance of commercial Pt/C counterpart. This in-depth understanding of the dealloying mechanism enriches our knowledge for the development of high-performance Pt-based alloy catalysts.

10.
Angew Chem Int Ed Engl ; 63(16): e202319936, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38372428

RESUMO

Revealing the dynamic reconstruction process and tailoring advanced copper (Cu) catalysts is of paramount significance for promoting the conversion of CO2 into ethylene (C2H4), paving the way for carbon neutralization and facilitating renewable energy storage. In this study, we initially employed density functional theory (DFT) and molecular dynamics (MD) simulations to elucidate the restructuring behavior of a catalyst under electrochemical conditions and delineated its restructuring patterns. Leveraging insights into this restructuring behavior, we devised an efficient, low-coordination copper-based catalyst. The resulting synthesized catalyst demonstrated an impressive Faradaic efficiency (FE) exceeding 70 % for ethylene generation at a current density of 800 mA cm-2. Furthermore, it showed robust stability, maintaining consistent performance for 230 hours at a cell voltage of 3.5 V in a full-cell system. Our research not only deepens the understanding of the active sites involved in designing efficient carbon dioxide reduction reaction (CO2RR) catalysts but also advances CO2 electrolysis technologies for industrial application.

11.
Nanoscale ; 16(6): 2868-2876, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38235504

RESUMO

The design of highly efficient and robust platinum-based electrocatalysts is pivotal for proton exchange membrane fuel cells (PEMFC). One of the long-standing issues for PEMFC is the rapid deactivation of the catalyst under working conditions. Here, we report a simple synthesis strategy for ultrafine PtCo alloy nanoparticles loaded on a unique carbon support derived from a zeolitic imidazolate framework-67 (ZIF-67) and Ketjen Black (KB) composite, exhibiting a remarkable catalytic performance toward the oxygen reduction reaction (ORR) and PEMFC. Benefitting from the N-doping and wide pore size distribution of the composite carbon supports, the growth of PtCo nanoparticles can be evenly restricted, leading to a uniform distribution. The Pt-integrated catalyst delivers an outstanding electrochemical performance with a mass activity that is 8.6 times higher than that of the commercial Pt/C catalyst. Impressively, the accelerated durability test (ADT) demonstrates that the hybrid carbon support can significantly enhance the durability. Theoretical simulations highlight the synergistic contribution between the supports and the PtCo nanoparticles. Moreover, hydrogen-oxygen fuel cells assembled with the catalyst exhibited a high power density of 1.83 W cm-2 at 4 A cm-2. These results provide a new opportunity to design advanced catalysts for PEMFC.

12.
Anal Chim Acta ; 1289: 342201, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38245204

RESUMO

Responsive hydrogels have received much attention for improving the detection performance of electrochemical sensors because of their special responsiveness. However, current responsive hydrogels generally suffer from long response times, ranging from tens of minutes to several hours. This situation severely limits the detection performance and practical application of electrochemical sensors. Here, an electrochemical sensing platform was constructed by employing dual-responsive polyacrylamide/zinc finger peptide/Fe-MOF hydrogel (PZFH) as the silent layer, sodium alginate-Ni2+-graphene oxide hydrogel as the signal layer. GOx@ZIF-8, as the immunoprobe, catalyzed glucose to H2O2 and gluconic acid, resulting in the cleavage of immunoprobe as the pH decreased and subsequent release of Zn2+ ions. During the process of Fe-MOF converting from Fe3+ to Fe2+, free radicals were generated and used to destroy the structure of the PZFH. Cysteine and histidine in the zinc finger peptide can specifically bind to Zn2+ to create many pores in PZFH, exposing the signal layer. These synergistic effects rapidly decreased the impedance of PZFH and increased the electrochemical signal of Ni2+. The electrochemical sensing platform was used to detect pro-gastrin-releasing peptide with response times as short as 7 min of PZFH, a wide linear range from 100 ng mL-1 to 100 fg mL-1, and an ultra-low limit of detection of 14.24 fg mL-1 (S/N = 3). This strategy will provide a paradigm for designing electrochemical sensors.


Assuntos
Resinas Acrílicas , Hidrogéis , Peróxido de Hidrogênio , Hidrogéis/química , Peróxido de Hidrogênio/química , Peptídeos , Dedos de Zinco , Técnicas Eletroquímicas/métodos
13.
Commun Biol ; 7(1): 119, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263256

RESUMO

Stimulus-induced conflicts in decision-making tasks produce both behavioral and neuronal congruency effects. However, how and when conflicts are detected and resolved at the neuronal level remains largely unclear. To address these issues, we recorded from single neurons in the frontal eye fields of two macaques performing a conflict task. Although the temporal dynamics of the neuronal congruency effects are independent of the specific task rules, they are substantially different in target- and distractor-encoding neurons. Conflicts were detected ~100 ms after the conflict-inducing cue (20-30 ms after the visual response), which is much faster than predicted based on human EEG results. This suggests that conflict detection relies on a fast mechanism in frontal eye fields. Resolving the conflict at the neuronal level, however, requires between <400 ms to ~1000 ms, and shows profound interindividual differences and depends on task rules, indicating that it is a more complex and top-down driven process. Our findings illuminate the neuronal mechanisms underlying decision-making when a conflict is present, a crucial cognitive process playing a role in basic survival and high-level cognitive functions.


Assuntos
Cognição , Lobo Frontal , Humanos , Animais , Macaca , Neurônios , Registros
14.
Nano Lett ; 24(4): 1197-1204, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38227967

RESUMO

Electrocatalytic reduction of nitrate to ammonia (NO3RR) is gaining attention for low carbon emissions and environmental protection. However, low ammonia production rate and poor selectivity have remained major challenges in this multi-proton coupling process. Herein, we report a facile strategy toward a novel Fe-based hybrid structure composed of Fe single atoms and Fe3C atomic clusters that demonstrates outstanding performance for synergistic electrocatalytic NO3RR. By operando synchrotron Fourier transform infrared spectroscopy and theoretical computation, we clarify that Fe single atoms serve as the active site for NO3RR, while Fe3C clusters facilitate H2O dissociation to provide protons (*H) for continued hydrogenation reactions. As a result, the Fe-based electrocatalyst exhibits ammonia Faradaic efficiency of nearly 100%, with a corresponding production rate of 24768 µg h-1 cm-2 at -0.4 V vs RHE, exceeding most reported metal-based catalysts. This research provides valuable guidance toward multi-step reactions.

15.
Nature ; 626(7997): 86-91, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297172

RESUMO

Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.

16.
Exp Dermatol ; 33(1): e14979, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37975615

RESUMO

Although a large number of existing studies have confirmed that people with vitiligo are prone to mental disorders, these observational studies may be subject to confounding factors and reverse causality, so the true causal relationship is inconclusive. We conducted a bidirectional Mendelian randomization (MR) analysis to assess the causality between vitiligo and mental disorders, namely depression, anxiety, insomnia, schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Summary statistics from large available genome-wide association study (GWAS) datasets for generalized vitiligo (n = 44 266), depression (n = 173 005), anxiety (n = 17 310), insomnia (n = 386 988), schizophrenia (n = 130 644), bipolar disorder (n = 413 466), OCD (n = 9725) and ADHD (n = 225 534) were utilized. Inverse-variance weighted (IVW), MR-Egger and weighted median were employed to estimate causal effects. Sensitivity analysis and MR Pleiotropy Residual Sum and Outliers (MR PRESSO) were conducted to assess heterogeneity and pleiotropy, ensuring the robustness of the results. Additionally, we corrected for estimating bias that might be brought on by sample overlap using MRlap. In our findings, none of the rigorous bidirectional MR analyses uncovered a significant causal association. Even after applying the MRlap correction, the effect sizes remained statistically nonsignificant, thereby reinforcing the conclusions drawn via IVW. In summary, our genetic-level investigation did not reveal a causal link between generalized vitiligo and mental disorders.


Assuntos
Transtornos Mentais , Distúrbios do Início e da Manutenção do Sono , Vitiligo , Humanos , Vitiligo/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos Mentais/genética
17.
Int J Cardiol ; 398: 131641, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065328

RESUMO

BACKGROUND: The MemoLefort is a new plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF). This study compares the safety and efficacy of MemoLefort and the well-established Watchman occluder for LAAC. METHODS: Between January 2021 and September 2022, a cohort of 189 consecutive patients who underwent LAAC with MemoLefort or Watchman at The Second Affiliated Hospital of Wenzhou Medical University were included. Patients with MemoLefort or Watchman devices were compared in terms of the primary safety endpoints encompassing major periprocedural complications and major bleeding events at follow-up, the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, and the combined hazard endpoint, a composite of all the above-mentioned hazards. RESULTS: Of the MemoLefort group (n = 83) and Watchman group (n = 106), the mean age, CHA2DS2-VASc score, and HAS-BLED score were 67.6 ± 9.2 vs. 69.0 ± 10.6 years, 3.9 ± 1.9 vs. 3.8 ± 1.9, and 1.6 ± 1.0 vs. 1.7 ± 1.2, respectively. After a median follow-up duration of 198 (99-329) vs. 334 (171-497) days, the primary endpoints of efficacy [2/49, 4.1% (MemoLefort) vs. 2/97, 2.1% (Watchman); hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.20-11.08; P = 0.68] and safety (1/49, 2.0% vs. 5/97, 5.2%; HR, 0.26; 95% CI, 0.05-1.31; P = 0.19), as well as the combined hazard endpoint (3/49, 61% vs. 6/97, 6.2%; HR, 0.70; 95% CI, 0.18-2.58; P = 0.59) were similar between groups. CONCLUSIONS: In the short term, LAAC with MemoLefort provided similar efficacy, safety, and net clinical benefit in comparison to Watchman devices.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Resultado do Tratamento , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Anticoagulantes
18.
J Am Chem Soc ; 146(1): 801-810, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38129385

RESUMO

Taxol is a potent drug used in various cancer treatments. Its complex structure has prompted extensive research into its biosynthesis. However, certain critical steps, such as the formation of the oxetane ring, which is essential for its activity, have remained unclear. Previous proposals suggested that oxetane formation follows the acetylation of taxadien-5α-ol. Here, we proposed that the oxetane ring is formed by cytochrome P450-mediated oxidation events that occur prior to C5 acetylation. To test this hypothesis, we analyzed the genomic and transcriptomic information for Taxus species to identify cytochrome P450 candidates and employed two independent systems, yeast (Saccharomyces cerevisiae) and plant (Nicotiana benthamiana), for their characterization. We revealed that a single enzyme, CYP725A4, catalyzes two successive epoxidation events, leading to the formation of the oxetane ring. We further showed that both taxa-4(5)-11(12)-diene (endotaxadiene) and taxa-4(20)-11(12)-diene (exotaxadiene) are precursors to the key intermediate, taxologenic oxetane, indicating the potential existence of multiple routes in the Taxol pathway. Thus, we unveiled a long-elusive step in Taxol biosynthesis.


Assuntos
Sistema Enzimático do Citocromo P-450 , Taxus , Sistema Enzimático do Citocromo P-450/metabolismo , Paclitaxel/metabolismo , Éteres Cíclicos , Catálise , Taxus/genética , Taxus/metabolismo
19.
Medicine (Baltimore) ; 102(49): e36457, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065860

RESUMO

To discuss the early changes of Glu and Cho in the affected areas of different types of subjective cognitive decline, including amnestic MCI (aMCl), non-amnestic MCI (naMCI) and vascular cognitive impairment no dementia (VCIND), using Proton Magnetic Resonance Spectroscopy (1H-MRS) technology. Routine head MRI and lH-MRS examinations were performed on 50 clearly diagnosed aMCI patients, 44 naMCI patients, 44 VCIND patients, and 44 elderly individuals with normal cognitive function. Measure the volume of the patient bilateral hippocampus. Using the bilateral hippocampus, left posterior cingulate gyrus (PCG), and frontal lobe as regions of interest, the scope under the peak of N-acetylaspartate (NAA), choline complex (Cho), glutamate (Glu), Metabolic Images (mI), and creatine (Cr) was tested. Perform a correlation analysis between the NAA/Cho/Cr values of the VCIND group and the MoCA score. All experimental subjects were right-handed. The NAACr values in both hippocampus of the VCIND were greatly lower than those in control (P < .05). The NAA/Cr values on both sides of the VCIND were correlated with the MoCA score (P < .05). The NAA/Cr values in the LHp and PCG of subjects in the aMCI and naMCI groups were lower than those in the NC group (P < .05). The NAA/Cr values in the left frontal lobe of the aMCI and naMCI showed no obvious decrease compared to the NC. The Glu/Cr of subjects in the aMCI was lower in the left PCG than those in the naMCI and NC (P < .05). The discrepancy between the naMCI and the NC was P > .05. In the LHp and frontal lobe, in contrast with the naMCI and NC, the mI/Cr values in the LHp and PCG of subjects in the aMCI were higher (P < .05). In the left frontal lobe, relative to the aMCI and NC, the mI/Cr values in the naMCI were higher (P < .05). The changes in the concentration of 1H-MRS metabolites in the hippocampus can indicate the presence of hippocampal neuronal damage before morphological changes occur in the hippocampus. 1H-MRS NAA/Cr can reflect the cognitive function changes of patients to a certain extent. There are regional differences in mI and Glu metabolism in the brain between aMCI and naMCI groups. 1H-MRS provides an effective basis for clinical differentiation between aMCI and naMCI.


Assuntos
Disfunção Cognitiva , Demência Vascular , Humanos , Idoso , Ácido Glutâmico/metabolismo , Relevância Clínica , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico , Colina , Ácido Aspártico , Creatina
20.
Proc Natl Acad Sci U S A ; 120(52): e2310916120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38117856

RESUMO

The kinetics and pathway of most catalyzed reactions depend on the existence of interface, which makes the precise construction of highly active single-atom sites at the reaction interface a desirable goal. Herein, we propose a thermal printing strategy that not only arranges metal atoms at the silica and carbon layer interface but also stabilizes them by strong coordination. Just like the typesetting of Chinese characters on paper, this method relies on the controlled migration of movable nanoparticles between two contact substrates and the simultaneous emission of atoms from the nanoparticle surface at high temperatures. Observed by in situ transmission electron microscopy, a single Fe3O4 nanoparticle migrates from the core of a SiO2 sphere to the surface like a droplet at high temperatures, moves along the interface of SiO2 and the coated carbon layer, and releases metal atoms until it disappears completely. These detached atoms are then in situ trapped by nitrogen and sulfur defects in the carbon layer to generate Fe single-atom sites, exhibiting excellent activity for oxygen reduction reaction. Also, sites' densities can be regulated by controlling the size of Fe3O4 nanoparticle between the two surfaces. More importantly, this strategy is applicable to synthesize Mn, Co, Pt, Pd, Au single-atom sites, which provide a general route to arrange single-atom sites at the interface of different supports for various applications.

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