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1.
Heliyon ; 10(11): e32630, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961923

RESUMO

Background and Purpose: Sex differences in acute ischemic stroke have been widely investigated, but the difference in acute ischemic stroke patients who received intravenous thrombolysis is not well understood. The current study was to investigate the issue based on a prospective cohort. Methods: From the Intravenous Thrombolysis Registry for Chinese Ischemic Stroke within 4.5h onset (INTRECIS) cohort, a total of 953 eligible patients with acute ischemic stroke were enrolled in final analysis. Based on 3-month modified Rankin scale score (mRS), patients were classified into good outcome group (mRS 0-1) and poor outcome group (mRS 2-6). Univariate and multivariate logistic regression analyses were used to identify predictive factors for clinical outcome in male or female patients. Results: Of the 953 patients treated with intravenous thrombolysis, 314 (32.9 %) were women. At day 90, we found no significant gender differences in good outcome (72.5 % vs 65.6 %, adjusted p = 0.414). We got the same results after propensity score matching (69.5 % vs 63.4 %, adjusted p = 0.637). Furthermore, we found that initial National Institute of Health Stroke Scale (NIHSS) score (odd ratio [OR] 0.877; 95 % CI 0.847-0.909, p < 0.001) and serum creatinine (OR 0.993; 95 % CI 0.986-1.000, p = 0 0.043) were found to be independent risk factors for poor outcome in male patients, while initial NIHSS score (OR 0.879; 95 % CI 0.839-0.920, p < 0.001), age (OR 0.970; 95 % CI 0.946-0.995, p = 0.017), systolic blood pressure (OR 0.984; 95 % CI 0.972-0.996, p = 0.007) and small artery occlusion (OR 2.718; 95 % CI 1.065-6.936, p = 0.036) in female patients. Conclusions: In this study, we found no gender difference in clinical outcome of thrombolysed stroke patients, but a difference in risk factors predicting outcome in male vs female patients was identified for the first time.

2.
Sci Rep ; 14(1): 15562, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971863

RESUMO

Systolic blood pressure variability (SBPV) is associated with outcome in acute ischemic stroke. Remote ischemic conditioning (RIC) has been demonstrated to be effective in stroke and may affect blood pressure. Relationship between SBPV and RIC treatment after stroke warrants investigation. A total of 1707 patients from per-protocol analysis set of RICAMIS study were included. The SBPV was calculated based on blood pressure measured at admission, Day 7, and Day 12. (I) To investigate the effect of SBPV on efficacy of RIC in stroke, patients were divided into High and Low categories in each SBPV parameter. Primary outcome was excellent functional outcome at 90 days. Compared with Control, efficacy of RIC in each category and interaction between categories were investigated. (II) To investigate the effect of RIC treatment on SBPV, SBPV parameters were compared between RIC and Control groups. Compared with Control, a higher likelihood of primary outcome in RIC was found in high category (max-min: adjusted risk difference [RD] = 7.2, 95% CI 1.2-13.1, P = 0.02; standard deviation: adjusted RD = 11.5, 95% CI 1.6-21.4, P = 0.02; coefficient of variation: adjusted RD = 11.2, 95% CI 1.4-21.0, P = 0.03). Significant interaction of RIC on outcomes were found between High and Low standard deviations (adjusted P < 0.05). No significant difference in SBPV parameters were found between treatment groups. This is the first report that Chinese patients with acute moderate ischemic stroke and presenting with higher SBPV, who were non-cardioemoblic stroke and not candidates for intravenous thrombolysis or endovascular therapy, would benefit more from RIC with respect to functional outcomes at 90 days, but 2-week RIC treatment has no effect on SBPV during hospital.


Assuntos
Pressão Sanguínea , Precondicionamento Isquêmico , AVC Isquêmico , Humanos , Masculino , Feminino , Pressão Sanguínea/fisiologia , Idoso , AVC Isquêmico/terapia , AVC Isquêmico/fisiopatologia , Pessoa de Meia-Idade , Precondicionamento Isquêmico/métodos , Resultado do Tratamento , Sístole/fisiologia
3.
Natl Sci Rev ; 11(7): nwae174, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38887544

RESUMO

Chemically modified superatoms have emerged as promising candidates in the new periodic table, in which Au13 and its doped M n Au13- n have been widely studied. However, their important counterpart, Ag13 artificial element, has not yet been synthesized. In this work, we report the synthesis of Ag13 nanoclusters using strong chelating ability and rigid ligands, that fills the gaps in the icosahedral superatomic metal clusters. After further doping Ag13 template with different degrees of Au atoms, we gained insight into the evolution of their optical properties. Theoretical calculations show that the kernel metal doping can modulate the transition of the excited-state electronic structure, and the electron transfer process changes from local excitation (LE) to charge transfer (CT) to LE. This study not only enriches the families of artificial superatoms, but also contributes to the understanding of the electronic states of superatomic clusters.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38831636

RESUMO

OBJECTIVE: We performed a post hoc exploratory analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to determine whether hypertension history and baseline systolic blood pressure (SBP) affect the efficacy of remote ischemic conditioning (RIC). METHODS: Based on the full analysis set of RICAMIS, patients were divided into hypertension versus non-hypertension group, or <140 mmHg versus ≥140 mmHg group. Each group was further subdivided into RIC and control subgroups. The primary outcome was modified Rankin Scale (mRS) 0-1 at 90 days. Efficacy of RIC was compared among patients with hypertension versus nonhypertension history and SBP of <140 mmHg versus ≥140 mmHg. Furthermore, the interaction effect of treatment with hypertension and SBP was assessed. RESULTS: Compared with control group, RIC produced a significantly higher proportion of patients with excellent functional outcome in the nonhypertension group (RIC vs. control: 65.7% vs. 57.0%, OR 1.45, 95% CI 1.06-1.98; p = 0.02), but no significant difference was observed in the hypertension group (RIC vs. control: 69.1% vs. 65.2%, p = 0.17). Similar results were observed in SBP ≥140 mmHg group (RIC vs. control: 68.0% vs. 61.2%, p = 0.009) and SBP <140 mmHg group (RIC vs. control: 65.6% vs. 64.7%, p = 0.77). No interaction effect of RIC on primary outcome was identified. INTERPRETATION: Hypertension and baseline SBP did not affect the neuroprotective effect of RIC, but they were associated with higher probability of excellent functional outcome in patients with acute moderate ischemic stroke who received RIC treatment.

5.
Appl Environ Microbiol ; : e0054324, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864627

RESUMO

In the field of chiral amine synthesis, ω-amine transaminase (ω-ATA) is one of the most established enzymes capable of asymmetric amination under optimal conditions. However, the applicability of ω-ATA toward more non-natural complex molecules remains limited due to its low transamination activity, thermostability, and narrow substrate scope. Here, by employing a combined approach of computational virtual screening strategy and combinatorial active-site saturation test/iterative saturation mutagenesis strategy, we have constructed the best variant M14C3-V5 (M14C3-V62A-V116S-E117I-L118I-V147F) with improved ω-ATA from Aspergillus terreus (AtATA) activity and thermostability toward non-natural substrate 1-acetylnaphthalene, which is the ketone precursor for producing the intermediate (R)-(+)-1-(1-naphthyl)ethylamine [(R)-NEA] of cinacalcet hydrochloride, showing activity enhancement of up to 3.4-fold compared to parent enzyme M14C3 (AtATA-F115L-M150C-H210N-M280C-V149A-L182F-L187F). The computational tools YASARA, Discovery Studio, Amber, and FoldX were applied for predicting mutation hotspots based on substrate-enzyme binding free energies and to show the possible mechanism with features related to AtATA structure, catalytic activity, and stability in silico analyses. M14C3-V5 achieved 71.8% conversion toward 50 mM 1-acetylnaphthalene in a 50 mL preparative-scale reaction for preparing (R)-NEA. Moreover, M14C3-V5 expanded the substrate scope toward aromatic ketone compounds. The generated virtual screening strategy based on the changes in binding free energies has successfully predicted the AtATA activity toward 1-acetylnaphthalene and related substrates. Together with experimental data, these approaches can serve as a gateway to explore desirable performances, expand enzyme-substrate scope, and accelerate biocatalysis.IMPORTANCEChiral amine is a crucial compound with many valuable applications. Their asymmetric synthesis employing ω-amine transaminases (ω-ATAs) is considered an attractive method. However, most ω-ATAs exhibit low activity and stability toward various non-natural substrates, which limits their industrial application. In this work, protein engineering strategy and computer-aided design are performed to evolve the activity and stability of ω-ATA from Aspergillus terreus toward non-natural substrates. After five rounds of mutations, the best variant, M14C3-V5, is obtained, showing better catalytic efficiency toward 1-acetylnaphthalene and higher thermostability than the original enzyme, M14C3. The robust combinational variant acquired displayed significant application value for pushing the asymmetric synthesis of aromatic chiral amines to a higher level.

7.
Mol Neurobiol ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850351

RESUMO

Microglia are the most important immune cells in the central nervous system (CNS), which can defend against external pathogens and stimuli. Dysregulation of microglia releases excessive proinflammatory cytokines and leads to neuroinflammation, which is fundamental to the pathophysiology of multiple neurological diseases. However, the molecular mechanisms underlying the regulation of proinflammatory cytokines in microglia are still not well-understood. Here, we identified that inhibitor of DNA binding protein 2 (Id2) was a negative regulator of tumor necrosis factor-α (TNFα) in cultured microglia. Knockdown of Id2 significantly increased the expression of TNFα in microglia, while overexpression of Id2 inhibited TNFα expression. Furthermore, by interacting with the p65 subunit of nuclear factor kappa-B (NF-κB), Id2 suppressed the transcription activation of NF-κB and inhibited TNFα expression. Interestingly, in lipopolysaccharides (LPS)-treated microglia, Id2 increased and underwent a cytoplasmic relocation. Immunoprecipitation and immunostaining results showed that by binding to the LIM domain of Id2, a scaffold protein PDZ and LIM 5 (PDLIM5) involved in the Id2 cytoplasmic relocation, which inactivated Id2 and resulted in higher TNFα expression in LPS-treated microglia. Collectively, our data delineate a novel effect of Id2 on TNFα regulation in microglia, which may shed a light on the proinflammatory cytokines regulating in microglia associated neuroimmune disorders.

8.
Neurotherapeutics ; : e00382, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852008

RESUMO

BACKGROUND: The ARAIS trial didn't demonstrate argatroban significantly improve functional outcome at 90 days in acute ischemic stroke. We conducted post hoc analysis of ARAIS to investigate whether baseline neurological deficit was associated with outcomes. METHODS: Patients without endovascular therapy who met screening criteria as protocol and completed argatroban treatment were enrolled and classified into two subgroups according to NIHSS score at admission. Primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0 to 1. Early neurological deterioration (END), defined as an increase of ≥4 in the NIHSS score from baseline within 48 hours, was investigated as secondary outcome. Compared with alteplase alone, we investigated treatment effect of argatroban plus alteplase on outcomes in subgroups and interaction with subgroups. RESULTS: A total of 675 patients from full analysis set were included: 390 were assigned into NIHSS score <10 subgroup and 285 into NIHSS score ≥10 subgroup. For primary outcome, there was similar treatment effect between argatroban plus alteplase and alteplase alone in NIHSS score ≥10 subgroup (adjusted RD, 5.8%; 95% CI, -6.0% to 17.5%; P = 0.33) and in NIHSS score <10 subgroup (adjusted RD, -1.4%; 95% CI, -9.9% to 7.1%; P = 0.75), and no significant interaction (P = 0.43). Occurrence of early neurological deterioration within 48 hours were significantly lower in NIHSS score ≥10 subgroup, compared with NIHSS score <10 subgroup (P = 0.006). CONCLUSION: Among patients with NIHSS score ≥10, argatroban plus alteplase could safely reduce END within 48 hours.

9.
Macromol Rapid Commun ; 45(13): e2400022, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704741

RESUMO

The preparation of self-healing polyurethane elastomers (PUEs) incorporating dynamic bonds is of considerable practical significance. However, developing a PUE with outstanding mechanical properties and high self-healing efficiency poses a significant challenge. Herein, this work has successfully developed a series of self-healing PUEs with various outstanding properties through rational molecular design. These PUEs incorporate m-xylylene diisocyanate and reversible dimethylglyoxime as hard segment, along with polytetramethylene ether glycol as soft segment. A significant amount of dynamic oxime-carbamate and hydrogen bonds are formed in hard segment. The microphase separated structure of the PUEs enables them to be colorless with a transparency of >90%. Owing to the chemical composition and multiple dynamic interactions, the PUEs are endowed with ultra-high tensile strength of 34.5 MPa, satisfactory toughness of 53.9 MJ m-3, and great elastic recovery both at low and high strains. The movement of polymer molecular chains and the dynamic reversible interactions render a self-healing efficiency of 101% at 70 °C. In addition, this self-healing polyurethane could still maintain high mechanical properties after recycling. This study provides a design strategy for the preparation of a comprehensive polyurethane with superior overall performance, which holds wide application prospects in the fields of flexible displays and solar cells.


Assuntos
Carbamatos , Elastômeros , Ligação de Hidrogênio , Oximas , Poliuretanos , Resistência à Tração , Poliuretanos/química , Oximas/química , Elastômeros/química , Carbamatos/química , Estrutura Molecular , Elasticidade
10.
J Pharm Biomed Anal ; 246: 116198, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754154

RESUMO

With the aging of the population, the prevalence of osteoporosis (OP) is rising rapidly, making it an important public health concern. Early screening and effective treatment of OP are the primary challenges facing the management of OP today. Quanduzhong capsule (QDZ) is a single preparation composed of Eucommia ulmoides Oliv., which is included in the Pharmacopoeia of the People's Republic of China. It is used to treat OP in clinical practice, but its mechanisms are unclear. This study involved 30 patients with OP, 30 healthy controls (HC), and 28 OP patients treated with QDZ to identify potential biomarkers for the early diagnosis of OP and to investigate the potential mechanism of QDZ in treating OP. The serum samples were analyzed using targeted amino acid metabolomics. Significant differences in amino acid metabolism were identified between the OP cohort and the HC group, as well as between OP patients before and after QDZ treatment. Compared with HC, the serum levels of 14 amino acids in OP patients changed significantly. Kynurenine, arginine, citrulline, methionine, and their combinations are expected to be potential biomarkers for OP diagnosis. Notably, QDZ reversed the changes in levels of 10 amino acids in the serum of OP patients and significantly impacted numerous metabolic pathways during the treatment of OP. This study focuses on screening potential biomarkers for the early detection of OP, which offers a new insight into the mechanism study of QDZ in treating OP.


Assuntos
Aminoácidos , Biomarcadores , Medicamentos de Ervas Chinesas , Metabolômica , Osteoporose , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Biomarcadores/sangue , Metabolômica/métodos , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Masculino , Aminoácidos/sangue , Idoso , Cápsulas , Eucommiaceae , Estudos de Casos e Controles , Adulto
11.
J Am Chem Soc ; 146(22): 15640-15647, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771765

RESUMO

Single-atom catalysts (SACs) have been widely investigated and have emerged as a transformative approach in electrocatalysis. Despite their clear structure, the origin of their exceptional activity remains elusive. Herein, we elucidate a common phenomenon of the hybridization state transition of metal centers, which is responsible for the activity origin across various SACs for different reactions. Focusing on N-doped carbon-supported Ni SAC (NiN4 SAC) for CO2 reduction reaction (CO2RR), our comprehensive computations successfully clarify the hybridization state transition under working conditions and its relation with the activity. This transition, triggered by the reaction intermediates and applied potential, converts the Ni center from the inert dsp2 hybridization state to the active d2sp3 hybridization state. Importantly, the calculated activity and selectivity of the CO2RR over the d2sp3-hybridized Ni center are consistent with the experimental results, offering strong support for the proposed hypothesis. This work suggests a universal principle of electronic structure evolution in SACs that could revolutionize catalyst design, which also introduces a new paradigm for manipulating electronic states to enhance catalytic performance, with implications for various reactions and catalyst platforms.

12.
ACS Nano ; 18(22): 14583-14594, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38722840

RESUMO

Direct photosynthesis of hydrogen peroxide (H2O2) from water and oxygen represents an intriguing alternative to the current indirect process involving the reduction and oxidation of quinones. However, limited light utilization and sluggish charge transfer largely impede overall photocatalytic efficiency. Herein, we present a heavily doped carbon nitride (CNKLi) nanocrystal for efficient and selective photoproduction of H2O2 via a two-electron oxygen reduction reaction (ORR) pathway. CNKLi induces metal-to-ligand charge transfer (MLCT) and electron trapping, which broadens the light absorption to the visible-near-infrared (vis-NIR) spectrum and prolongs the photoelectron lifetime to the microsecond time scale with an exceptional charge diffusion length of ∼1200 nm. Near-unit photoutilization with an apparent quantum yield (AQY) of 100% for H2O2 generation is achieved below 420 nm. Impressively, CNKLi exhibits an appreciable AQY of 16% at 700 nm, which reaches the absorption capacity (∼16%), thus suggesting a near-unit photon utilization <700 nm. In situ characterization and theoretical calculations reveal the facilitated charge transfer from K+ to the heptazine ring skeleton. These findings provide an approach to improve the photosynthetic efficiency of direct H2O2 preparation in the vis-NIR region and expand applications for driving kinetically slow and technologically desirable oxidations or high-value chemical generation.

13.
BMC Pediatr ; 24(1): 307, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711038

RESUMO

BACKGROUND: Anorectal malformation is a common congenital problem occurring in 1 in 5,000 births and has a spectrum of anatomical presentations, requiring individualized surgical treatments for normal growth. Delayed extubation or reintubation may result in a longer intensive care unit (ICU) stay and hospital stay, increased mortality, prolonged duration of mechanical ventilation, increased tracheostomy rate, and higher hospital costs. Extensive studies have focused on the role of risk factors in early extubation during major infant surgery such as Cardiac surgery, neurosurgery, and liver surgery. However, no study has mentioned the influencing factors of delayed extubation in neonates and infants undergoing angioplasty surgery. MATERIALS AND METHODS: We performed a retrospective study of neonates and infants who underwent anorectal malformation surgery between June 2018 and June 2022. The principal goal of this study was to observe the incidence of delayed extubation in pediatric anorectal malformation surgery. The secondary goals were to identify the factors associated with delayed extubation in these infants. RESULTS: We collected data describing 123 patients who had anorectal malformations from 2019 to 2022. It shows that 74(60.2%) in the normal intubation group and 49(39.8%) in the longer extubation. In the final model, anesthesia methods were independently associated with delayed extubation (P < 0.05). CONCLUSION: We found that the anesthesia method was independently associated with early extubation in neonates and infants who accepted pediatric anorectal malformation surgery.


Assuntos
Extubação , Malformações Anorretais , Humanos , Estudos Retrospectivos , Fatores de Risco , Feminino , Masculino , Recém-Nascido , Lactente , Fatores de Tempo , Malformações Anorretais/cirurgia , Períneo/cirurgia
14.
J Hazard Mater ; 472: 134498, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38733782

RESUMO

Advanced oxidation processes for the treatment of organic pollutants in wastewater suffer from difficulties in mineralization, potential risks of dissolved residues, and high oxidant consumption. In this study, radical-initiated polymerization is dominated in an UV/peroxydisulfate (PDS) process to eliminate organic pollutant of pharmaceutical metoprolol (MTP). Compared with an ideal degradation-based UV/PDS process, the present process can save four fifths of PDS consumption at the same dissolved organic carbon removal of 47.3%. Simultaneously, organic carbon can be recovered from aqueous solution by separating solid polymers at a ratio of 50% of the initial chemical oxygen demand. The chemical structure of products was analyzed to infer the transformation pathways of MTP. Unlike previous studies on simple organic pollutants that the polymerization can occur independently, the polymerization of MTP is dependent on the partial degradation of MTP, and the main monomer in polymerization is a dominant degradation product (4-(2-methoxyethyl)-phenol, denoted as DP151). The separated solid polymers are formed by repeated oxidation and coupling of DP151 or its derivatives through a series of intermediate oligomers. This proof-of-concept study demonstrates the advantage of polymerization-dominated mechanism on dealing with large organic molecules with complex structures, as well as the potential of UV/PDS process for simultaneous organic pollution reduction and organic carbon recovery from aqueous solution.

15.
High Alt Med Biol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743636

RESUMO

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 00:00-00, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

16.
Front Genet ; 15: 1385293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818040

RESUMO

Background: Varicose veins (VV) are a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment. Methods: This study conducted Summary-data-based Mendelian Randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies and cis-expression quantitative trait loci databases. Only genes with PP.H4 > 0.7 in colocalization were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization (MR) analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies and The Drug-Gene Interaction Database data to identify and screen the remaining genes and identified four drug targets for the treatment of VV. Results: We identified four genes significantly associated with VV, namely, KRTAP5-AS1 [Odds ratio (OR) = 1.08, 95% Confidence interval (CI): 1.05-1.11, p = 1.42e-10] and PLEKHA5 (OR = 1.13, 95% CI: 1.06-1.20, p = 6.90e-5), CBWD1 (OR = 1.05, 95% CI: 1.01-1.11, p = 1.42e-2) and CRIM1 (OR = 0.87, 95% CI: 0.81-0.95, p = 3.67e-3). Increased expression of three genes, namely, KRTAP5-AS1, PLEKHA5, and CBWD1, was associated with increased risk of the disease, and increased expression of CRIM1 was associated with decreased risk of the disease. These four genes could be targeted for VV therapy. Conclusion: We identified four potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that KRTAP5-AS1, PLEKHA5, CBWD1, and CRIM1 might be potential drug targets for varicose veins.

17.
Angew Chem Int Ed Engl ; : e202407887, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802322

RESUMO

Circularly polarized light (CPL) detection is of great significance in various applications such as drug identification, sensing and imaging. Atomically precise chiral metal nanoclusters with intense circular dichroism (CD) signals are promising candidates for CPL detection, which can further facilitate device miniaturization and integration. Herein, we report the preparation of a pair of optically active chiral silver nanoclusters [Ag7(R/S-DMA)2(dpppy)3] (BF4)3 (R/S-Ag7) for direct CPL detection. The crystal structure and molecular formula of R/S-Ag7 clusters are confirmed by single-crystal x-ray diffraction and high-resolution mass spectrometry. R/S-Ag7 clusters exhibit strong CD spectra and CPL luminescence both in solution and solid states. When used as the photoactive materials in photodetectors, R/S-Ag7 enables effective discrimination between left-handed circularly polarized and right-handed circularly polarized light at 520 nm with short response time, high responsivity and considerable discrimination ratio. This study is the first report on using atomically precise chiral metal nanoclusters for CPL detection.

18.
Fitoterapia ; 176: 105973, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38663560

RESUMO

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention.


Assuntos
Clostridioides difficile , Diarreia , Microbioma Gastrointestinal , Extratos Vegetais , Scutellaria baicalensis , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Diarreia/microbiologia , Diarreia/tratamento farmacológico , Camundongos , Scutellaria baicalensis/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Masculino , Infecções por Clostridium/tratamento farmacológico , Modelos Animais de Doenças , RNA Ribossômico 16S/genética , Camundongos Endogâmicos C57BL , Colo/microbiologia
19.
RSC Adv ; 14(16): 11358-11367, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38595708

RESUMO

Half-calcined dolomites (HCDs) have been widely used in environmental remediation, medicine, and construction. However, advanced calcination technologies are required to modify their microstructure and thus improve their working performance. Herein, we investigated the effects of a variety of inorganic salts on the decomposition of dolomite based on thermogravimetric, compositional, and morphological analysis. The thermogravimetric data showed that certain salts significantly lowered the half-decomposition temperature of dolomite, which included LiCl, CaCl2, MgCl2, AlCl3, LiNO3, KNO3, K2CO3, Li2CO3, Li2SO4, Na3PO4, and K3PO4. Compositional analysis demonstrated that only half-decomposition occurred when salt-bearing dolomite was calcined at a temperature of 723-923 K, leading to the formation of CaO-free HCDs composed of periclase and Mg-calcite having a Mg level of 2.0-10.5 mol%. Morphological analysis showed that porous HCDs were feasibly obtained by calcining salt-bearing dolomite at 723-923 K. MgO coarsening occurred at a temperature above 873 K, but it could be avoided by controlling the calcination time. The mechanism of salts may be related to the heterovalent doping effect, which may lead to an increase in the concentration of vacancies in the dolomite lattice.

20.
J Colloid Interface Sci ; 667: 22-31, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38615620

RESUMO

Recently, there has been a significant increase in interest in using photocatalysis for the energy conversion of polluting gases. In this research, sodium and ruthenium bimetallic functional sites co-modified bismuth tungstate (Ru/Na-Bi2WO6) nanoflower photocatalyst was synthesized via the hydrothermal method. The CO2 reduction products on the Bi2WO6 substrate were CO (1.66 µmol/g/h, 68 %) and CH4 (0.78 µmol/g/h, 32 %). After optimization, a significant change in the CO2 products of the Bi2WO6-based composite material was observed, with CO (0.61 µmol/g/h, 3.6 %) and CH4 (16.1 µmol/g/h, 96.4 %). Results showed that the dominance of CH4 as the main product in the Ru/Na-BWO system is attributed to the effective doping of Na, which generates impurity energy levels composed of oxygen vacancies, lowering the conduction band position of Bi2WO6, thereby suppressing CO generation, and enhancing CH4 selectivity by changing the CO2 activation pathway. The remarkable performance is ascribed to the synergized adsorption and activation of CO2 by the tandem Na+ sites and Ru0 sites. Specifically, the doped Na+ sites play a major role in promoting the adsorption CO2 molecules, while the Ru0 sites play a dominant role in facilitating the activation of the intermediates.

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