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1.
Adv Mater ; : e2312920, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39385647

RESUMO

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

2.
Ecotoxicol Environ Saf ; 285: 117126, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39369664

RESUMO

Heterogeneous catalyst-mediated sulfate radical-based advanced oxidation processes (SR-AOPs) showed excellent performance during antibiotics degradation. Spinel was a promising catalyst for SR-AOPs, but the secondary contamination due to metal ions leaching needed to be addressed. And the destruction of catalyst structure could lead to the reduction of catalytic activity and the difficulty of recovery. Thus, a novel nitrogen-doped carbon (NC)-supported CoFe2O4 (CoFe2O4@NC) was synthesized as the activator of PMS for sulfadiazine (SDZ) degradation under low Co leaching conditions. The consequences indicated that the CoFe2O4@NC/PMS system exhibited higher PMS decomposition efficiency and reaction stoichiometry efficiency than the bare CoFe2O4/PMS systems (CoFe2O4-180 and CoFe2O4-800), which in turn demonstrated a better SDZ removal performance. Under the condition of CoFe2O4@NC dosage 0.1 g/L, PMS concentration 0.5 mM, solution pH 6.8 and temperature 25°C, SDZ (20 mg/L) was almost completely degraded within 60 min. XPS analysis showed that the NC not only protected and stabilized CoFe2O4, but also provided additional active sites for PMS activation. During SDZ degradation, SO4•-, HO•, •O2- and 1O2 were involved in the reaction, among which SO4• and HO• made the main contribution. Meanwhile, CoFe2O4@NC could be recovered by magnetic separation, and showed great stability (Co leaching 0.852 mg/L) and reusability. In the fifth cycle experiment, 85.02 % SDZ degradation was obtained. Based on the detected intermediates (12 intermediates were identified) and DFT calculations, possible degradation pathways for SDZ in CoFe2O4@NC/PMS were proposed. The condensed dual descriptor indicated that the N7, N11, and C15 atoms on SDZ molecule were the main sites of electrophilic attack, which was consistent with the detected intermediates. The degradation of SDZ involved hydroxylation of NH2, cleavage of S-N and extrusion of SO2. This study explored the improvements made in NC support material to catalytic performance and resistance to dissolution of spinel, providing new insights for subsequent researches.


Assuntos
Carbono , Cobalto , Compostos Férricos , Indóis , Nitrogênio , Peróxidos , Polímeros , Sulfadiazina , Poluentes Químicos da Água , Sulfadiazina/química , Cobalto/química , Peróxidos/química , Carbono/química , Nitrogênio/química , Indóis/química , Polímeros/química , Poluentes Químicos da Água/química , Catálise , Compostos Férricos/química , Oxirredução , Antibacterianos/química
3.
Brain Res Bull ; 218: 111097, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395778

RESUMO

Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases.

4.
Sci Rep ; 14(1): 23350, 2024 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375437

RESUMO

Although some studies have revealed the association between bullying victimization and internet addiction in adolescents, the mediating and moderating factors between the two need to be further discussed. This study aimed to discuss the chain mediating role of anxiety and inhibitory control between bullying victimization and internet addiction among Chinese adolescents. A cross-sectional study was conducted in seven schools in five provinces of China by convenience sampling from February to March 2024. A total of 1673 participants (695 boys and 978 girls) with an average age of 15.86 ± 0.74 years were included in this study. Subjective data on bullying victimization, internet addiction, anxiety, inhibitory control were collected and analyzed, and a mediation model test was carried out. After controlling for age and gender, bullying victimization was found to be a significant predictor of internet addiction (ß = 0.098, p < 0.001). However, when anxiety and inhibitory control were added, the predictive effect was no longer significant (ß = 0.006, p > 0.05). Bullying victimization can predict internet addiction through anxiety and inhibitory control. It is suggested that guardians should provide adequate support to adolescent bullying victims in order to reduce the negative impact of bullying victimization on adolescents and prevent the occurrence of internet addiction.


Assuntos
Ansiedade , Bullying , Vítimas de Crime , Transtorno de Adição à Internet , Humanos , Adolescente , Masculino , Feminino , Transtorno de Adição à Internet/psicologia , Transtorno de Adição à Internet/epidemiologia , Bullying/psicologia , Bullying/estatística & dados numéricos , Ansiedade/epidemiologia , Ansiedade/psicologia , Vítimas de Crime/psicologia , Estudos Transversais , China/epidemiologia , Internet , Comportamento do Adolescente/psicologia , Comportamento Aditivo/psicologia , Comportamento Aditivo/epidemiologia
5.
Sci Rep ; 14(1): 24881, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438570

RESUMO

Driven by emerging research paradigms, the application of artificial intelligence models presents innovative tools for designing materials and optimizing their performance. In the field of materials science, there is a current research emphasis on exploring techniques for characterizing material structures to achieve precise descriptions. This paper proposes a crystal graph convolution neural network model that incorporates a tripartite interaction approach. The model not only incorporates atomic information, bond lengths, and bond angles but also offers a method for updating atoms and bond lengths, facilitating accurate descriptions of crystal structures by capturing implicit structural information. Focusing on predicting the formation energy of crystalline compounds, our results demonstrate improved predictive accuracy compared to existing representation algorithms. The average error of the formation energy in the random dataset, demonstrating robust generalization, is merely 0.048eV/atom, with an impressive R 2 value of 0.994. Additionally, this paper establishes a crystal graph neural network framework for predicting algorithm performance. By integrating automatic parallel algorithms and an automated process, we achieve a synthesis of these techniques, enhancing computational efficiency and streamlining algorithm usage.

6.
BMC Pregnancy Childbirth ; 24(1): 674, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39407169

RESUMO

BACKGROUND: The severe postpartum hemorrhage (SPPH) leads to dangerous maternal conditions, and its rate is still increasing and the trend in related risk factors is changing. Placenta-related problems remain the high-risk factor for SPPH. The object is to investigate the prevalence and the risk factors of the severe postpartum hemorrhage in pregnant women with placenta previa or low-lying placenta. METHOD: A retrospective analysis of pregnant women with placenta previa or low-lying placenta after 28 weeks gestation from May 2018 to May 2023 in the Peking Union Medical College Hospital was conducted. The primary outcome was severe postpartum hemorrhage defined as blood loss ≥ 1000 mL within 24 h of childbirth, or with signs or symptoms of low blood volume requiring transfusion of ≥ 4U of red blood cells. Univariate and multivariate logistic regression were used to identify potential risk factors of severe postpartum hemorrhage and receiver operating curve to evaluate the prediction performance. RESULTS: Of the 14,964 women, 201 met the inclusive criteria. SPPH rate was 1.3% overall and 18.9% in women with placenta previa or low-lying placenta. Weight (aOR = 0.93, 95%CI 0.87-0.99), increta or percreta placenta (aOR = 7.93, 95%CI 2.53-24.77) were the risk factors. The area under the ROC curve was 0.69(95%CI 0.59-0.80) for increta or percreta placenta alone, and 0.72(95%CI 0.62-0.82) for the combination of times of cesarean sections and anterior placenta. CONCLUSIONS: Placenta accreta spectrum was the key independent risk factor of SPPH in women with placenta previa or low-lying placenta. Antenatal risk assessment of SPPH in these population is highly desirable and optimal intervention could be planned.


Assuntos
Placenta Prévia , Hemorragia Pós-Parto , Humanos , Feminino , Gravidez , Placenta Prévia/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto , China/epidemiologia , Placenta Acreta/epidemiologia , Índice de Gravidade de Doença , Prevalência
7.
Medicine (Baltimore) ; 103(42): e40157, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39432594

RESUMO

As an anti-inflammatory and antioxidant, vitamin K has the potential to reduce telomere attrition. However, the correlation between dietary vitamin K and telomere length (TL) has not been reported. We aimed to investigate the association between these 2 variables. This study included 3754 participants from the National Health and Nutrition Examination Survey 2001-2002 database. We used multivariate linear regression and restricted cubic splines to assess the relationship between dietary vitamin K intake and TL. Subgroup analyses and interaction tests were utilized to examine the stability of the results. After adjusting for all variables, each unit increase in daily dietary intake of vitamin K lengthened telomeres by 0.22 base pairs (ß = 0.22, 95% CI: 0.09-0.36, P = .001). Individuals with the highest dietary vitamin K intake had significantly longer TL (ß = 80.27, 95% CI: 20.83-139.71, P = .008). Subgroup analyses suggested that this association persisted in populations stratified by gender, age, diabetes, cardiovascular disease (CVD), body mass index and total energy intake (P for interaction > .05). A linear relationship between dietary vitamin K intake and TL was observed in restricted cubic splines (P for nonlinear = .554). In conclusion, our findings suggest that dietary vitamin K intake is positively associated with TL, providing recent evidence to guide the management of healthy diets.


Assuntos
Dieta , Inquéritos Nutricionais , Telômero , Vitamina K , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Telômero/efeitos dos fármacos , Vitamina K/administração & dosagem , Dieta/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Índice de Massa Corporal
8.
J Control Release ; 376: 1-19, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39343142

RESUMO

Aggregation-induced emission luminogens (AIEgens) possess the unique property of enhanced fluorescence and photostability in aggregated states, making them exceptional materials for the convergence of imaging and phototherapy. With their inherent advantages, AIEgens are propelling the field of nanomedicine into a vibrant frontier in the phototheranostics of a spectrum of diseases, particularly in the realm of cancer immunotherapy. AIEgens-based therapeutics enhance the cancer immune response through a variety of approaches, including real-time image-guided precise therapy, induction of programmed cell death, metabolic reprogramming, and modulation of the tumor microenvironment. Additionally, they contribute to the synergistic effect of immune checkpoint inhibition, a pivotal aspect of modern cancer immunotherapy strategies. This review offers a comprehensive overview of the integration of AIEgens in nanomedicine and their role in immune adaptation, highlighting the advantages, basic action mechanisms, and recent advancement of AIEgens as promising therapeutic platform for cancer immunotherapy.

9.
Nanoscale ; 16(40): 19042-19047, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39308360

RESUMO

As a new generation of display technology, micro-light-emitting diodes (micro-LEDs) have been widely recognized owing to their excellent performance in brightness, contrast ratio, resolution, etc. This work proposes a continuous wave (CW) laser writing strategy to achieve perovskite quantum dots (PQDs) array with small pixel size and pitch, overcoming the processing difficulties and limitations of mass transfer. Since PQDs have highly dynamic surface ligand states and low ionic bond energy, suitable laser power can quench PQDs and form an array area. The use of low-power CW lasers in the laser direct writing process, on the one hand, greatly maintains the luminescence performance and edge flatness of each PQD array, and the pixel pitch (1.5 µm-9 µm)/size can be adjusted arbitrarily, which meets the high-resolution micro-display requirements. On the other hand, we found that after the low-power laser quenches the PQDs, its residual oxide can absorb photons, thus reducing the backlight leakage in color conversion micro-LEDs. Finally, red/green/blue three-color conversion micro-LED and laser projection displays were realized; these results provide a feasible strategy for next-generation micro-LED displays.

10.
Psychol Res Behav Manag ; 17: 3147-3157, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39280038

RESUMO

Background: Suicide is a global public health issue. This study examined the role of COVID-19 burnout and reappraisal in suicidal ideation caused by depressive symptoms among Chinese college students. Methods: 587 students (261 boys, M age = 19.53, SD = 1.42) were assessed using the Short Depression-Happiness Scale (SDHS), Positive and Negative Suicide Ideation (PANSI) inventory, and Emotion Regulation Scale (ERS). Results: Correlation analysis indicated depressive symptoms were negatively correlated with reappraisal and positively correlated with suicidal ideation and COVID-19 burnout. Reappraisal was negatively correlated with suicidal ideation and COVID-19 burnout. The moderated mediation model showed COVID-19 burnout enhanced the direct effect of depressive symptoms on suicidal ideation and indirectly enhanced this effect by weakening the protective role of reappraisal. Conclusion: These finding show that reappraisal acts as a protective factor against suicidal ideation in individuals with depressive symptoms, while COVID-19 burnout exacerbates this effect by weakening reappraisal's protective role.

11.
BMC Med ; 22(1): 362, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227921

RESUMO

BACKGROUND: Obesity and metabolic syndrome (MetS) have become urgent worldwide health problems, predisposing patients to unfavorable myocardial status and thyroid dysfunction. Low-carbohydrate diet (LCD) and time-restricted eating (TRE) have been confirmed to be effective methods for weight management and improving MetS, but their effects on the myocardium and thyroid are unclear. METHODS: We conducted a secondary analysis in a randomized clinical diet-induced weight-loss trial. Participants (N = 169) diagnosed with MetS were randomized to the LCD group, the 8 h TRE group, or the combination of the LCD and TRE group for 3 months. Myocardial enzymes and thyroid function were tested before and after the intervention. Pearson's or Spearman's correlation was assessed between functions of the myocardium and thyroid and cardiometabolic parameters at baseline. RESULTS: A total of 162 participants who began the trial were included in the intention-to-treat (ITT) analysis, and 57 participants who adhered to their assigned protocol were involved in the per-protocol (PP) analysis. Relative to baseline, lactate dehydrogenase, creatine kinase MB, hydroxybutyrate dehydrogenase, and free triiodothyronine (FT3) declined, and free thyroxine (FT4) increased after all 3 interventions (both analyses). Creatine kinase (CK) decreased only in the TRE (- 18 [44] U/L, P < 0.001) and combination (- 22 [64] U/L, P = 0.003) groups (PP analysis). Thyrotropin (- 0.24 [0.83] µIU/mL, P = 0.011) and T3 (- 0.10 ± 0.04 ng/mL, P = 0.011) decreased in the combination group (ITT analysis). T4 (0.82 ± 0.39 µg/dL, P = 0.046), thyroglobulin antibodies (TgAb, 2 [1] %, P = 0.021), and thyroid microsomal antibodies (TMAb, 2 [2] %, P < 0.001) increased, while the T3/T4 ratio (- 0.01 ± 0.01, P = 0.020) decreased only in the TRE group (PP analysis). However, no significant difference between groups was observed in either analysis. At baseline, CK was positively correlated with the visceral fat area. FT3 was positively associated with triglycerides and total cholesterol. FT4 was negatively related to insulin and C-peptide levels. TgAb and TMAb were negatively correlated with the waist-to-hip ratio. CONCLUSIONS: TRE with or without LCD confers remarkable metabolic benefits on myocardial status and thyroid function in subjects with MetS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475822.


Assuntos
Dieta com Restrição de Carboidratos , Síndrome Metabólica , Glândula Tireoide , Humanos , Síndrome Metabólica/dietoterapia , Masculino , Feminino , Dieta com Restrição de Carboidratos/métodos , Pessoa de Meia-Idade , Adulto , Miocárdio/metabolismo , Testes de Função Tireóidea , Idoso
12.
Sci Total Environ ; 954: 176316, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293763

RESUMO

Constructing bird habitat networks (BHNs) is crucial for maintaining the health and service equilibrium of urban ecosystems, especially in large metropolitan areas where the pressure of urbanization is intense. However, most existing BHNs fail to account for the dynamic changes and unique requirements of local species, leading to homogenized construction outcomes and ecological corridor objectives. This study employs a comprehensive approach to identify bird habitat patches using multiple high-quality sources, then utilize circuit theory and complex network theory to construct and assess the resilience of BHN. Our key findings showed: (1)93 bird habitat sources were identified, predominantly situated in the continuous green spaces of southern and southeastern Shanghai, whereas habitat sources in the city center and other densely built-up areas are more dispersed, highlighting them as prime targets for future ecological restoration efforts. (2) The distribution of bird habitat corridors exhibits significant spatial heterogeneity, with primary corridors predominantly spanning the southwestern and eastern parts of the study area, while secondary corridors are more abundant in the western and northern parts, forming a denser network, whereas the central area shows fewer and more isolated corridors. (3) The decline in structural and functional resilience was notably more rapid under targeted attacks than under random attacks, underscoring the need to prioritize crucial bird habitat sources on the city's periphery, especially near highly urbanized areas, in urban planning and biodiversity conservation efforts to sustain ecological balance and biodiversity. These insights provide a crucial scientific basis for urban planners, emphasizing the integration of biodiversity conservation into urban development strategies by optimizing ecological sources and corridors to balance development with ecological preservation.

13.
ACS Appl Mater Interfaces ; 16(36): 48094-48102, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39189509

RESUMO

Lead halide perovskite anion exchange reactions tend to be spontaneous and rapid. To achieve precise control of anion exchange and modulate the bandgaps of perovskites to meet the demands in full-color displays, a laser-induced liquid-phase anion exchange method is developed in this paper. CsPbBr3 perovskites embedded in a polymer matrix are converted to CsPb(BrxCl1-x)3 and CsPb(BrxI1-x)3 perovskites, realizing the shift from green fluorescence to blue and red fluorescence. By changing the laser parameters, the anion exchange extent and luminescence wavelength are precisely tuned, with the maximum tuning wavelength range of 431-696 nm. Due to the focusing properties of the laser, the spatial position of anion exchange can be precisely controlled, which is significant for realizing fast and accurate patterning without masks. Based on this method, blue patterns with different light-emitting wavelengths are fabricated. RGB three-color patterns on a single perovskite composite film are successfully prepared by further replacement of halogen ions. More importantly, the polymer matrix provides ultraflexibility and good stability for the films; even if the composite films are arbitrarily folded or repeatedly bent, they can still maintain good luminous intensity. This method will show great potential in the field of flexible, full-color displays.

14.
Front Endocrinol (Lausanne) ; 15: 1414509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39211452

RESUMO

Objective: The aim of this study was to evaluate the effectiveness of burosumab therapy in children with X-Linked Hypophosphatemia (XLH). Materials and methods: We systematically reviewed literature from PubMed, Web of Science, The Cochrane Library, and Embase up until January 2024, using EndNote Web for study organization. The Newcastle-Ottawa scale guided quality assessment, while Revman software was used for data analysis and visualization. Study selection, quality evaluation, and data aggregation were independently performed by three researchers. Results: The meta-analysis encompassed ten studies, including eight cohort studies that examined burosumab's impact pre- and post-administration, and two randomized controlled trials comparing burosumab to standard therapy. The evidence from this review suggests burosumab's superiority in managing XLH in pediatric populations, particularly in improving key biochemical markers including 1,25-dihydroxyvitamin D (1,25-(OH)2D), phosphorus, and alkaline phosphatase (ALP), alongside improvements in the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), and significant skeletal improvements as indicated by the rickets severity score (RSS) and the 6-minute walk test (6MWT). However, the long-term safety and effects, including height and quality of life (QOL) data, remains to be elucidated. Conclusions: Burosumab has shown significant therapeutic effectiveness in treating children with XLH, highlighting its potential as a key treatment option.


Assuntos
Anticorpos Monoclonais Humanizados , Raquitismo Hipofosfatêmico Familiar , Humanos , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Criança , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento
15.
Comput Biol Med ; 181: 109028, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39173485

RESUMO

Despite extensive algorithms for epilepsy prediction via machine learning, most models are tailored for offline scenarios and cannot handle actual scenarios where data changes over time. Catastrophic forgetting(CF) for learned electroencephalogram(EEG) data occurs when EEG changes dynamically in the clinical setting. This paper implements a continual learning(CL) strategy Memory Projection(MP) for epilepsy prediction, which can be combined with other algorithms to avoid CF. Such a strategy enables the model to learn EEG data from each patient in dynamic subspaces with weak correlation layer by layer to minimize interference and promote knowledge transfer. Regularization Loss Reconstruction Algorithm and Matrix Dimensionality Reduction Algorithm are introduced into the core of MP. Experimental results show that MP exhibits excellent performance and low forgetting rates in sequential learning of seizure prediction. The forgetting rate of accuracy and sensitivity under multiple experiments are below 5%. When learning from multi-center datasets, the forgetting rates for accuracy and sensitivity decrease to 0.65% and 1.86%, making it comparable to state-of-the-art CL strategies. Through ablation experiments, we have analyzed that MP can operate with minimal storage and computational cost, which demonstrates practical potential for seizure prediction in clinical scenarios.


Assuntos
Eletroencefalografia , Aprendizado de Máquina , Convulsões , Humanos , Eletroencefalografia/métodos , Convulsões/fisiopatologia , Algoritmos , Processamento de Sinais Assistido por Computador , Epilepsia/fisiopatologia
16.
J Am Chem Soc ; 146(28): 19460-19473, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38959398

RESUMO

Dirhodium tetrakis(2,2'-binaphthylphosphate) catalysts were successfully developed for asymmetric C-H functionalization with trichloroethyl aryldiazoacetates as the carbene precursors. The 2,2'-binaphthylphosphate (BNP) ligands were modified by introduction of aryl and/or chloro functionality at the 4,4',6,6' positions. As the BNP ligands are C2-symmetric, the resulting dirhodium tetrakis(2,2'-binaphthylphosphate) complexes were expected to be D4-symmetric, but X-ray crystallographic and computational studies revealed this is not always the case because of internal T-shaped CH-π and aryl-aryl interactions between the ligands. The optimum catalyst is Rh2(S-megaBNP)4, with 3,5-di(tert-butyl)phenyl substituents at the 4,4' positions and chloro substituents at the 6,6' positions. This catalyst adopts a D4-symmetric arrangement and is ideally suited for site-selective C-H functionalization at unactivated tertiary sites with high levels of enantioselectivity, outperforming the best dirhodium tetracarboxylate catalyst developed for this reaction. The standard reactions were conducted with a catalyst loading of 1 mol % but lower catalyst loadings can be used if desired, as illustrated in the C-H functionalization of cyclohexane in 91% ee with 0.0025 mol % catalyst loading (29,400 turnover numbers). These studies further illustrate the effectiveness of donor/acceptor carbenes in site-selective intermolecular C-H functionalization and expand the toolbox of catalysts available for catalyst-controlled C-H functionalization.

17.
J Inflamm Res ; 17: 4791-4810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39051052

RESUMO

Background: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes. Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed. Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol. Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.

18.
J Pharm Biomed Anal ; 249: 116339, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39024794

RESUMO

Codonopsis Radix (CR), a traditional tonic medicinal material in China, has been proven to possess a variety of bioactive functions. However, its chemical composition and in vivo metabolic pattern have not been fully elucidated. In this study, AB-8 macroporous resin column chromatography was employed for the enrichment of small molecular components in CR. Furthermore, a method combining ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry with Acquire X intelligent data acquisition technology software was developed for the preliminary screening and identification of the chemical composition of CR in vitro and their metabolites in vivo. As a result, a total of 116 components were preliminarily characterized in the CR extract, including 28 polyacetylenes, 33 organic acids, 4 amino acids, 23 alkaloids, 9 phenylpropanoids, 6 terpenoids, 2 nucleosides, and 11 others. Additionally, a total of 84 compounds, including 37 prototype components and 47 metabolites, were identified in the plasma, urine, and feces of rats after oral administration of CR. Specifically, 11, 24, 19, 32, and 25 constituents were identified in the heart, liver, spleen, lung, and kidney, respectively. Of note, the lung and spleen are the organs with the highest distribution of CR compounds. These findings will serve as valuable data for future research on the correlation between the chemical composition and pharmacological effects of CR.


Assuntos
Codonopsis , Medicamentos de Ervas Chinesas , Animais , Ratos , Administração Oral , Alcaloides/análise , Alcaloides/química , Cromatografia Líquida de Alta Pressão/métodos , Codonopsis/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Fezes/química , Espectrometria de Massas/métodos , Metaboloma , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Raízes de Plantas/química , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Distribuição Tecidual
19.
Ultrason Sonochem ; 109: 106996, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39032371

RESUMO

Extraction of coconut paring oil (CPO) from processing by-products adds value to the product and reduces resource wastage. This study aims to assess the impact of 20 kHz, 20/80 kHz and 20/40/80 kHz of multi-frequency ultrasonic-assisted enzymatic extraction (MFUAEE) on the yield, physicochemical properties, fatty acid composition, total phenolic content, antioxidant activity, and emulsion stability of CPO derived from wet coconut parings (WCP). Results revealed that the CPO extraction yield with MFUAEE was 32.58 % - 43.31 % higher compared to AEE. The tri-frequency 20/40/80 kHz mode of multi-frequency ultrasound pretreatment exhibited the highest CPO extraction yield (70.08 %). The oil extracted through MFUAEE displayed similar fatty acid profiles to AEE, but had lower peroxide value, K232 and K270 values. Particularly, MFUAEE oil contained higher total phenolic content and exhibited potent DPPH free radical scavenging capacity. Results observed by SEM indicated that the pretreatment with multi-frequency ultrasound more efficiently disrupts the cellular structure of the WCP. Additionally, MFUAEE enhanced emulsion stability through the cavitation effect of ultrasound. These findings suggest that MFUAEE is a valuable approach for method for obtaining CPO with elevated extraction yield and superior quality, thereby enhancing the utilization of coconut by-products.


Assuntos
Óleo de Coco , Cocos , Emulsões , Ondas Ultrassônicas , Óleo de Coco/química , Cocos/química , Antioxidantes/isolamento & purificação , Antioxidantes/química , Fenômenos Químicos , Fracionamento Químico/métodos , Ácidos Graxos/química , Fenóis/isolamento & purificação , Fenóis/química
20.
Seizure ; 120: 180-188, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39029408

RESUMO

OBJECTIVE: To expand the clinical phenotype and mutation spectrum of familial mesial temporal lobe epilepsy (FMTLE) and provide a new perspective for exploring the pathological mechanisms of epilepsy caused by leucine-rich glioma inactivated 1 (LGI1) variants. METHODS: We reported clinical data from two families with FMTLE and screened patients for variants in the LGI1 gene using Whole-exome sequencing and Sanger sequencing. The clinical features of FMTLE were analysed. The pathogenicity of the causative loci was assessed according to the American College of Medical Genetics and Genomics guidelines, and potential pathogenic mechanisms were predicted through multiple bioinformatics and molecular dynamics software. RESULTS: We identified two novel LGI1 truncating variants within two large families with FMTLE: LGI1 (c.1174C>T, p.Q392X) and LGI1 (c.703C>T, p.Q235X). Compared to previous reports, we found that focal to bilateral tonic-clonic seizures are a common type of seizure in FMTLE. The clinical phenotypes of patients with FMTLE caused by LGI1 variants were relatively mild, and all patients responded well to valproic acid. Bioinformatics analyses and molecular dynamics simulations showed that protein structure and interactions were considerably weakened or damaged as a result of both variants. CONCLUSION: This study presents the first report identifying LGI1 as a potential novel pathogenic gene within FMTLE families, thereby broadening the mutation spectrum associated with FMTLE. The findings of this study offer novel insights and avenues for understanding the intricate molecular mechanisms underlying LGI1 variants and their correlations with patient phenotypes. This study proposes the possibility of familial focal epilepsy syndromes overlapping.


Assuntos
Epilepsia do Lobo Temporal , Peptídeos e Proteínas de Sinalização Intracelular , Linhagem , Fenótipo , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/congênito , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Criança , Adolescente
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