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1.
J Am Chem Soc ; 146(19): 13546-13557, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690842

RESUMO

Glycidic esters represent pivotal constituents in synthetic chemistry, offering enhanced versatility for tailoring toward a diverse array of molecular targets in comparison with simple epoxides. While considerable progress has been made in the asymmetric synthesis of trans- and trisubstituted glycidic esters, achieving enantioselective preparation of cis-glycidic esters has remained a long-standing challenge. Here, we demonstrate a selectivity-predictable modular platform for the asymmetric synthesis of cis-glycidic esters via a novel dinuclear (salen)titanium(III)-catalyzed radical-type kinetic resolution (KR) approach. This radical KR protocol operates under mild conditions and demonstrates a wide substrate scope, facilitating the synthesis of alkyl- and aryl-substituted cis-glycidic esters with high levels of regioselectivity and enantioselectivity, along with hydroxy ester byproducts representing synthetically valuable motifs as well. This study presents a unique exploration of radical-type KR applied to epoxides, effectively overcoming the steric challenges inherent in conventional nucleophilic-type methodologies typically employed in epoxide chemistry.

2.
J Transl Med ; 22(1): 19, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178171

RESUMO

BACKGROUND: Macrophages phenotypic deviation and immune imbalance play vital roles in pregnancy-associated diseases such as spontaneous miscarriage. Trophoblasts regulate phenotypic changes in macrophages, however, their underlying mechanism during pregnancy remains unclear. Therefore, this study aimed to elucidate the potential function of trophoblast-derived miRNAs (miR-410-5p) in macrophage polarization during pregnancy. METHODS: Patient decidual macrophage tissue samples in spontaneous abortion group and normal pregnancy group (those who had induced abortion for non-medical reasons) were collected at the Reproductive Medicine Center of Renmin Hospital of Wuhan University from April to December 2021. Furthermore, placental villi and decidua tissue samples were collected from patients who had experienced a spontaneous miscarriage and normal pregnant women for validation and subsequent experiments at the Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), from March 2021 to September 2022. As an animal model, 36 female mice were randomly divided into six groups as follows: naive-control, lipopolysaccharide-model, agomir-negative control prevention, agomir-410-5p prevention, agomir-negative control treatment, and agomir-410-5p treatment groups. We analyzed the miR-410-5p expression in abortion tissue and plasma samples; and supplemented miR-410-5p to evaluate embryonic absorption in vivo. The main source of miR-410-5p at the maternal-fetal interface was analyzed, and the possible target gene, signal transducer and activator of transcription (STAT) 1, of miR-410-5p was predicted. The effect of miR-410-5p and STAT1 regulation on macrophage phenotype, oxidative metabolism, and mitochondrial membrane potential was analyzed in vitro. RESULTS: MiR-410-5p levels were lower in the spontaneous abortion group compared with the normal pregnancy group, and plasma miR-410-5p levels could predict pregnancy and spontaneous abortion. Prophylactic supplementation of miR-410-5p in pregnant mice reduced lipopolysaccharide-mediated embryonic absorption and downregulated the decidual macrophage pro-inflammatory phenotype. MiR-410-5p were mainly distributed in villi, and trophoblasts secreted exosomes-miR-410-5p at the maternal-fetal interface. After macrophages captured exosomes, the cells shifted to the tolerance phenotype. STAT1 was a potential target gene of miR-410-5p. MiR-410-5p bound to STAT1 mRNA, and inhibited the expression of STAT1 protein. STAT1 can drive macrophages to mature to a pro-inflammatory phenotype. MiR-410-5p competitive silencing of STAT1 can avoid macrophage immune disorders. CONCLUSION: MiR-410-5p promotes M2 macrophage polarization by inhibiting STAT1, thus ensuring a healthy pregnancy. These findings are of great significance for diagnosing and preventing spontaneous miscarriage, providing a new perspective for further research in this field.


Assuntos
Aborto Espontâneo , MicroRNAs , Humanos , Feminino , Gravidez , Camundongos , Animais , Aborto Espontâneo/genética , Aborto Espontâneo/metabolismo , Placenta/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Lipopolissacarídeos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Trofoblastos/metabolismo , Transdução de Sinais/genética , Macrófagos/metabolismo
3.
Inorg Chem ; 63(5): 2606-2615, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38267390

RESUMO

The pre-transmetalation intermediates are critically important in Suzuki-Miyaura cross-coupling (SMC) reactions and have become a hot spot of the current research. However, the pre-transmetalation intermediates under base-free conditions have not been clear. Herein, a comprehensive theoretical study is performed on the base-free Pd-catalyzed desulfonative SMC reaction. The fragile coordination feature and the acceleration role of the RuPhos chelate ligand are revealed. The hydrogen-bond complex between the Pd-F complex and aryl boronic acid is identified as an important pre-transmetalation intermediate, which increases the energy span to 32.5 kcal/mol. The controlling factor for the formation of the hydrogen-bond complexes is attributed to the electronegativities of halogen atoms in the metal halide complexes. What is more, other reported SMC reaction systems involving metal halide complexes and aryl boronic acids are reconsidered and suggest that the hydrogen-bond complexes widely exist as stable pre-transmetalation intermediates with influencing the catalytic activities. The earth-abundant Ni-catalyzed desulfonative SMC reaction is further designed and predicted to have a higher activity than the original Pd-catalyzed SMC reaction.

4.
Eur J Nutr ; 63(4): 1293-1314, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38403812

RESUMO

PURPOSE: The previous studies that examined the effectiveness of unsupervised machine learning methods versus traditional methods in assessing dietary patterns and their association with incident hypertension showed contradictory results. Consequently, our aim is to explore the correlation between the incidence of hypertension and overall dietary patterns that were extracted using unsupervised machine learning techniques. METHODS: Data were obtained from Japanese male participants enrolled in a prospective cohort study between August 2008 and August 2010. A final dataset of 447 male participants was used for analysis. Dimension reduction using uniform manifold approximation and projection (UMAP) and subsequent K-means clustering was used to derive dietary patterns. In addition, multivariable logistic regression was used to evaluate the association between dietary patterns and the incidence of hypertension. RESULTS: We identified four dietary patterns: 'Low-protein/fiber High-sugar,' 'Dairy/vegetable-based,' 'Meat-based,' and 'Seafood and Alcohol.' Compared with 'Seafood and Alcohol' as a reference, the protective dietary patterns for hypertension were 'Dairy/vegetable-based' (OR 0.39, 95% CI 0.19-0.80, P = 0.013) and the 'Meat-based' (OR 0.37, 95% CI 0.16-0.86, P = 0.022) after adjusting for potential confounding factors, including age, body mass index, smoking, education, physical activity, dyslipidemia, and diabetes. An age-matched sensitivity analysis confirmed this finding. CONCLUSION: This study finds that relative to the 'Seafood and Alcohol' pattern, the 'Dairy/vegetable-based' and 'Meat-based' dietary patterns are associated with a lower risk of hypertension among men.


Assuntos
Dieta , Hipertensão , Aprendizado de Máquina , Humanos , Masculino , Hipertensão/epidemiologia , Japão/epidemiologia , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Dieta/métodos , Dieta/estatística & dados numéricos , Estudos de Coortes , Adulto , Fatores de Risco , Comportamento Alimentar , Padrões Dietéticos , População do Leste Asiático
5.
Environ Res ; 249: 118497, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38365054

RESUMO

Developing a photoelectric cathode capable of efficiently activating molecular oxygen to degrade pollutants is a coveted yet challenging goal. In pursuit of this, we synthesize a Fe doped porous carbon nitride catalyst (Fe-CN) using an ionothermal strategy and subsequently loaded it on the hydrophobic carbon felt (CF) to fabricate the Fe-CN/CF photoelectric cathode. This cathode benefits from the synergistic effects between the porous CN support and the highly dispersed Fe species, which enhance O2 absorption and activation. Additionally, the hydrophobic CF serves as a gas diffusion layer, accelerating O2 mass transfer. These features enable the Fe-CN/CF cathode to demonstrate notable photoelectrocatalytic (PEC) degradation efficiency. Specifically, under optimal conditions (cathodic bias of -0.3 VAg/AgCl, pH 7, and a catalyst loading of 3 mg/cm2), the system achieves a 76.4% removal rate of tetracycline (TC) within 60 min. The general application potential of this system is further underscored by its ability to remove approximately 98% of 4-chlorophenol (4-CP) and phenol under identical conditions. Subsequent investigations into the active species and degradation pathways reveal that 1O2 and h+ play dominant role during the PEC degradation process, leading to gradually breakdown of TC into less toxicity, smaller molecular intermediates. This work presents a straightforward yet effective strategy for constructing efficient PEC systems that leverage molecular oxygen activation to degrade pollutants.


Assuntos
Carbono , Ferro , Nitrilas , Oxigênio , Nitrilas/química , Oxigênio/química , Carbono/química , Ferro/química , Catálise , Poluentes Químicos da Água/química , Porosidade , Interações Hidrofóbicas e Hidrofílicas , Eletrodos , Técnicas Eletroquímicas/métodos
6.
Int J Mol Sci ; 25(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38791115

RESUMO

Surface chemistry and bulk structure jointly play crucial roles in achieving high-performance supercapacitors. Here, the synergistic effect of surface chemistry properties (vacancy and phosphorization) and structure-derived properties (hollow hydrangea-like structure) on energy storage is explored by the surface treatment and architecture design of the nanostructures. The theoretical calculations and experiments prove that surface chemistry modulation is capable of improving electronic conductivity and electrolyte wettability. The structural engineering of both hollow and nanosheets produces a high specific surface area and an abundant pore structure, which is favorable in exposing more active sites and shortens the ion diffusion distance. Benefiting from its admirable physicochemical properties, the surface phosphorylated MnCo2O4.5 hollow hydrangea-like structure (P-MnCoO) delivers a high capacitance of 425 F g-1 at 1 A g-1, a superior capability rate of 63.9%, capacitance retention at 10 A g-1, and extremely long cyclic stability (91.1% after 10,000 cycles). The fabricated P-MnCoO/AC asymmetric supercapacitor achieved superior energy and power density. This work opens a new avenue to further improve the electrochemical performance of metal oxides for supercapacitors.


Assuntos
Capacitância Elétrica , Compostos de Manganês , Óxidos , Oxigênio , Compostos de Manganês/química , Óxidos/química , Oxigênio/química , Propriedades de Superfície , Nanoestruturas/química , Técnicas Eletroquímicas/métodos
7.
Molecules ; 29(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38930964

RESUMO

Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by amphiphilic solutes. This comprehensive review explores state-of-the-art techniques for characterizing microemulsions, which are versatile solutions essential across various industries, such as pharmaceuticals, food, and petroleum. This article delves into spectroscopic methods, nuclear magnetic resonance, small-angle scattering, dynamic light scattering, conductometry, zeta potential analysis, cryo-electron microscopy, refractive index measurement, and differential scanning calorimetry, examining each technique's strengths, limitations, and potential applications. Emphasizing the necessity of a multi-technique approach for a thorough understanding, it underscores the importance of integrating diverse analytical methods to unravel microemulsion structures from molecular to macroscopic scales. This synthesis provides a roadmap for researchers and practitioners, fostering advancements in microemulsion science and its wide-ranging industrial applications.

8.
ACS Org Inorg Au ; 4(2): 258-267, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38585511

RESUMO

The industrial production of methanol through CO hydrogenation using the Cu/ZnO/Al2O3 catalyst requires harsh conditions, and the development of new catalysts with low operating temperatures is highly desirable. In this study, organic biomimetic FLP catalysts with good tolerance to CO poison are theoretically designed. The base-free catalytic reaction contains the 1,1-addition of CO into a formic acid intermediate and the hydrogenation of the formic acid intermediate into methanol. Low-energy spans (25.6, 22.1, and 20.6 kcal/mol) are achieved, indicating that CO can be hydrogenated into methanol at low temperatures. The new extended aromatization-dearomatization effect involving multiple rings is proposed to effectively facilitate the rate-determining CO 1,1-addition step, and a new CO activation model is proposed for organic catalysts.

9.
Bioresour Technol ; 399: 130595, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493936

RESUMO

Poplar is widely used in the paper industry and accompanied by abundant branches waste, which is potential feedstock for bioethanol production. Acid-chlorite pretreatment can selectively remove lignin, thereby significantly increasing enzymatic efficiency. Moreover, lignin residues valorization via gasification-syngas fermentation can achieve higher fuel yield. Herein, environmental and economic aspects were conducted to assess technological routes, which guides further process optimization. Life cycle assessment results show that wood-based biorefineries especially coupling scenarios have significant advantages in reducing global warming potential in contrast to fossil-based automotive fuels. Normalization results indicate that acidification potential surpasses other indicators as the primary impact category. In terms of economic feasibility, coupling scenarios present better investment prospects. Bioethanol yield is the most critical factor affecting market competitiveness. Minimum ethanol selling price below ethanol international market price is promising with higher-levels technology. Further work should be focused on technological breakthrough, consumable reduction or replacement.


Assuntos
Etanol , Lignina , Animais , Lignina/química , Etanol/química , Madeira/metabolismo , Biotecnologia/métodos , Fermentação , Estágios do Ciclo de Vida
10.
ACS Omega ; 9(17): 19148-19157, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38708247

RESUMO

The long-term prognosis of nonsmall cell lung cancer (NSCLC) remains unsatisfactory, which is a major challenge in lung cancer treatment. BIRC3 is an inhibitor of apoptosis (IAP) protein that contributes to tumor regulation. However, the underlying regulatory mechanisms of BIRC3 in NSCLC remains unknown. We initiated an analysis of BIRC3 expression data in NSCLC tumors and adjacent tissues using the TCGA and GEO databases and examined the variations in prognosis. Further, we conducted overexpression (OE) and knockdown (KD) studies on BIRC3 to evaluate its effects on NSCLC cell proliferation, migration, and invasion. Additionally, through utilization of a nude mouse model, the regulatory effects of BIRC3 on NSCLC were verified in vivo. Co-immunoprecipitation (Co-IP) assay served to pinpoint the proteins with which BIRC3 interacts. The results indicated that BIRC3 is down-regulated in NSCLC tissues and that patients with high BIRC3 expression demonstrate a better prognosis. BIRC3 is a tumor suppressor, inhibiting the proliferation and metastasis of NSCLC. Co-IP results revealed that BIRC3 interacts with HSP90B1, leading to a decrease in HSP90B1 expression and subsequent negative regulation of the ERK signaling pathway. BIRC3 may serve as a prognostic biomarker for NSCLC. It directly interacts with HSP90B1 to negatively regulate the ERK signaling pathway, thereby hindering the progression of NSCLC.

11.
Clin Ophthalmol ; 18: 1851-1860, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948340

RESUMO

Background: To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO). Methods: This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 µm at month 12. Results: 33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 (t = 4.221, P = 0.000; and t = 4.834, P = 0.000) with no significant difference between the two groups (t = 0.071, P = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 µm (t = 8.261, P = 0.000) compared to 431.36 ± 294.55 (t = 8.413, P = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups (t = 0.053, P = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred. Conclusion: Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group. Trial Registration: The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).

12.
Open Life Sci ; 19(1): 20220807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299010

RESUMO

Branches covering (BC) is a way to reuse the pruned branches and save the cost of ground cloth. This study investigated the effects of BC and ground-cloth covering on the soil microcosm environment by measuring the chemical properties and microbial communities at different soil depths for 6 years. The results revealed that BC significantly improved soil chemical properties, increased the abundance of bacterial microbial communities and the diversity and homogeneity of bacteria and fungi, while decreased the abundance of fungal microbial communities. There was a threshold value for the regulation of microbial communities by BC, which decreased the high-abundance communities (Proteobacteria, Ascomycota, etc.) and increased the low-abundance communities (Acidobacteriota, Basidiomycota, etc.). Fungi were more sensitive to BC than bacteria. The stability and homogeneity of microorganisms were stronger in the 15-25 cm soil layer. The bacterial phyla were dominated by Proteobacteria, with the top 10 phyla accounting for more than 80% of the relative abundance; the genera were dominated by MND1, with the top 10 genera accounting for about 10%. The fungal phyla were dominated by Ascomycota, with the top 10 phyla accounting for 50-90%; the genera were dominated by unidentified Pyronemataceae sp., with the top 10 genera accounting for 30-60%. The phyla that differed significantly between treatments were mainly Proteobacteria, Ascomycota, Acidobacteriota, and Basidiomycota. In addition, metabolism was the predominant function in bacteria, while Saprotroph was the predominant function in fungi. Bacteroidota correlated strongly with soil chemical properties and bacterial functions, while Chytridiomycota correlated strongly with soil chemical properties and Pathogen-Saprotroph-Symbiotroph. In conclusion, BC can improve soil nutrient content and optimize microbial community structure and function. Through initially assessing the effects of BC on soil nutrients and microorganisms in pear orchard rows, this study provides a reference for excavating key microorganisms and updating the soil row management model.

13.
J Orthop Surg Res ; 19(1): 198, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528538

RESUMO

PURPOSE: This study aimed to evaluate the protective effects of gentiopicroside against lipopolysaccharide-induced chondrocyte inflammation. METHODS: SW 1353 chondrosarcoma cells were stimulated with LPS (5 µg/ml) for 24 h and treated with different concentrations of gentiopicroside (GPS) for 24 h. The toxic effects of GPS on chondrocytes were determined using a CCK-8 assay and EdU staining. Western blotting, qPCR, and immunofluorescence analysis were used to examine the protective effect of GPS against the inflammatory response in chondrocytes induced by lipopolysaccharide (LPS). One-way ANOVA was used to compare the differences between the groups (significance level of 0.05). RESULTS: The CCK-8 results showed that 10, 20 and 40 µM GPS had no significant toxic effects on chondrocytes; GPS effectively reduced the production of IL-1ß and PGE2, reversed LPS-induced extracellular matrix degradation in cartilage by inhibiting the Stat3/Runx2 signaling pathway, and suppressed the hypertrophic transformation of SW 1353 chondrosarcoma cells. CONCLUSION: Our study demonstrated that GPS significantly inhibited the LPS-induced inflammatory response and hypertrophic cellular degeneration in SW 1353 chondrosarcoma cells and is a valuable traditional Chinese medicine for the treatment of knee osteoarthritis.


Assuntos
Condrossarcoma , Glucosídeos Iridoides , Osteoartrite , Humanos , Condrócitos/metabolismo , Lipopolissacarídeos/toxicidade , Osteoartrite/metabolismo , Sincalida/metabolismo , Sincalida/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Hipertrofia , Condrossarcoma/tratamento farmacológico , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo
14.
Sci Rep ; 14(1): 7991, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580792

RESUMO

In sustaining arch locked-segment-type slopes, natural soil arches play a key anti-sliding role in the slope's evolution. In this study, a self-developed model test device was used to simulate the whole process of deformation evolution of sustaining arch locked-segment-type slopes, and the formation of natural sustaining arch and its locking control effect on slope stability were studied. The test results show that the continuous formation and progressive destruction of the sustaining arch were observed. The sustaining arch formed in the second time has the best locking effect, and the anti-sliding force reaches its stress peak point. However, the slope is not in a critically unstable state, instead, the stress is continuously adjusted to form a larger range of soil arch to resist the slope thrust. Consequently, the slope destabilizes until the ultimate shear strength of arch foots is exceeded, at which point the critical arch height of the arch is reached. The critical arch height mechanical model for slope stability analysis was developed based on the soil arching effect and limit equilibrium theory. The applicability of the model was demonstrated by the physical test and Xintan slope data, which can provide some guidance for early warning of landslides.

15.
Sci Rep ; 14(1): 5044, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424156

RESUMO

The significance means of the seismic reinforcement effect of a pile-anchor system for slope reinforcement has been widely recognized. However, cases of deformation failure and instability sliding of the pile-anchor system itself and the reinforced slope under seismic action continue to be recorded. Therefore, it is crucial to evaluate the seismic performance of slopes reinforced by a pile-anchor system to prevent the system's failure. Current evaluation models of a slope reinforced by a pile-anchor system mainly focus on slope stability; however, the safety of the pile-anchor system itself is not sufficiently considered in these models. Consequently, in this study, we propose a multi-objective optimization evaluation (MOE) model for evaluating the seismic performance of slopes reinforced by a pile-anchor system that considers slope stability, safety of the pile-anchor system, and dynamic response of the slope. This model considers slope displacement, acceleration amplification factor of a slope, pile displacement, and anchor displacement as negative indexes, and anti-slide pile bending moment, shear force, and anchor axial force as intermediate indexes. The comprehensive weight of relevant indexes is obtained by combining subjective and objective weights, and the seismic reinforcement effect of the pile-anchor system is evaluated subsequently. In conclusion, the MOE model proposed in this study provides a novel solution for the optimization evaluation of a slope reinforced by a pile-anchor system in forthcoming projects.

16.
Gait Posture ; 108: 177-182, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38100956

RESUMO

BACKGROUND: Children with unilateral spastic cerebral palsy (USCP) have muscle hypertonia, balance, and coordination defects that affect gross motor skills, especially walking. Understanding the gait characteristics and lower limb muscle activation patterns of USCP children can provide an objective and quantitative basis for patient assessment and treatment plan formulation. OBJECTIVE: This study compared the gait and lower limb muscle activation characteristics of children with USCP and with typical development (TD) during walking. METHODS: We recorded gait and sEMG data of 20 children with USCP, and 20 with typical development. sEMG signals were acquired from the bilateral tibialis anterior (TA) and lateral gastrocnemius muscles (LG) during walking. The root mean square (RMS) value, integrated electromyographic (iEMG) value and co-contraction ratio (CR) were used to evaluate muscle activity. Student's t Test and non-parametric rank sum Test were used to compare the differences between the data groups (significance level of 0.05). RESULTS: The stance time, step length, speed, single leg support time ratio, ground impact, pre-swing angle, and muscle strength of the affected side were significantly decreased compared to those of the unaffected side in children with USCP (P < 0.05), while the swing phase, muscle tonus of LG were significantly prolonged (P < 0.05). Compared with TD children, children with USCP exhibited reduced bilateral walking ability, particularly noticeable in their smaller pre-swing angle(P < 0.05), diminished muscle strength of the TA and LG, as well as LG spasms(P < 0.05). SIGNIFICANCE: Children with USCP have decreased ambulatory gait stability. Step length, pull acceleration, pre-swing angle, and CR can be used as sensitive indicators for gait assessment. Strengthening the TA muscle and reducing ankle spasm may help improve gait and postural stability in children with USCP.


Assuntos
Paralisia Cerebral , Criança , Humanos , Paralisia Cerebral/complicações , Marcha/fisiologia , Caminhada/fisiologia , Extremidade Inferior , Músculo Esquelético/fisiologia , Eletromiografia
17.
Eur J Med Chem ; 275: 116577, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38875809

RESUMO

Sphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2. Molecular dynamics simulations suggest that the incorporation of larger substitution groups facilitates a more effective occupation of the binding site, thereby stabilizing the complex. Compared to the widely used inhibitor ABC294640, compound 12q exhibits superior anti-proliferative activity against various cancer cells, inducing G2 phase arrest and apoptosis in liver cancer cells HepG2. Notably, 12q inhibited migration and colony formation in HepG2 and altered intracellular sphingolipid content. Moreover, intraperitoneal administration of 12q in mice resulted in decreased levels of S1P. 12q provides a valuable tool compound for exploring the therapeutic potential of targeting SphK2 in cancer.


Assuntos
Acetamidas , Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Fosfotransferases (Aceptor do Grupo Álcool) , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Humanos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Acetamidas/farmacologia , Acetamidas/síntese química , Acetamidas/química , Estrutura Molecular , Apoptose/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Descoberta de Drogas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química
18.
Eur J Med Chem ; 271: 116408, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38621327

RESUMO

As an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, including palmitoyltransferases and depalmitoylases, and discusses the currently available broad-spectrum and selective inhibitors for these enzymes.


Assuntos
Aciltransferases , Lipoilação , Bibliotecas de Moléculas Pequenas , Humanos , Aciltransferases/metabolismo , Aciltransferases/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Estrutura Molecular , Proteínas/metabolismo , Proteínas/química
19.
J Phys Chem Lett ; 15(9): 2301-2310, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38386516

RESUMO

The brain's function can be dynamically reconfigured through a unified neuron-synapse architecture, enabling task-adaptive network-level topology for energy-efficient learning and inferencing. Here, we demonstrate an organic neuristor utilizing a ferroelectric-electrolyte dielectric interface. This neuristor enables tunable short- to long-term plasticity and reconfigurable logic-in-memory functions by controlling the interfacial interaction between electrolyte ions and ferroelectric dipoles. Notably, the short-term plasticity of the organic neuristor allows for power-efficient reservoir computing in edge-computing scenarios, exhibiting impressive recognition accuracy, including images (90.6%) and acoustic signals (97.7%). For high-performance computing tasks, the neuristor based on long-term plasticity and logic-in-memory operations can construct all of the hardware circuits of a binarized neural network (BNN) within a unified framework. The BNN demonstrates excellent noise tolerance, achieving high recognition accuracies of 99.2% and 86.4% on the MNIST and CIFAR-10 data sets, respectively. Consequently, our research sheds light on the development of power-efficient artificial intelligence systems.

20.
ACS Appl Mater Interfaces ; 16(14): 17506-17516, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38538567

RESUMO

Although the conversion of O2 and H2O to H2O2 over graphite carbon nitride (g-C3N4) has been realized by means of the photocatalytic process, the catalytic activity of pristine g-C3N4 is still restricted by the rapid charge recombination and inadequate exposure of the active site. In this work, we propose a straightforward strategy to solve these limitations by decreasing the thickness and improving the crystallinity of g-C3N4, resulting in the preparation of few-layered crystalline carbon nitride (FL-CCN). Benefiting from the minimal thickness and highly ordered in-plane triangular cavities within the structure, FL-CCN processes an extended π-conjugated system with a reduced charge transfer resistance and expanded specific surface area. These features accelerate the efficiency of photogenerated charge separation in FL-CCN and contribute to explore of its surface active sites. Consequently, FL-CCN exhibits a significantly improved H2O2 evolution rate (63.95 µmol g-1 h-1), which is 7.8 times higher than that of pristine g-C3N4 (8.15 µmol g-1 h-1), during the photocatalytic conversion of O2 and H2O. This systematic investigation offers valuable insights into the mechanism of photocatalytic H2O2 generation and the development of efficient catalysts.

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