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1.
Proc Natl Acad Sci U S A ; 120(39): e2308435120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37733739

RESUMO

GPR34 is a functional G-protein-coupled receptor of Lysophosphatidylserine (LysoPS), and has pathogenic roles in numerous diseases, yet remains poorly targeted. We herein report a cryo-electron microscopy (cryo-EM) structure of GPR34 bound with LysoPS (18:1) and Gi protein, revealing a unique ligand recognition mode with the negatively charged head group of LysoPS occupying a polar cavity formed by TM3, 6 and 7, and the hydrophobic tail of LysoPS residing in a lateral open hydrophobic groove formed by TM3-5. Virtual screening and subsequent structural optimization led to the identification of a highly potent and selective antagonist (YL-365). Design of fusion proteins allowed successful determination of the challenging cryo-EM structure of the inactive GPR34 complexed with YL-365, which revealed the competitive binding of YL-365 in a portion of the orthosteric binding pocket of GPR34 and the antagonist-binding-induced allostery in the receptor, implicating the inhibition mechanism of YL-365. Moreover, YL-365 displayed excellent activity in a neuropathic pain model without obvious toxicity. Collectively, this study offers mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, and provides proof of concept that targeting GPR34 represents a promising strategy for disease treatment.


Assuntos
Inibição Psicológica , Neuralgia , Humanos , Microscopia Crioeletrônica , Ligação Competitiva
2.
Funct Integr Genomics ; 24(2): 63, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517555

RESUMO

The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Expressão Gênica , RNA Mensageiro , Biomarcadores , Proteínas com Motivo Tripartido/genética , Fatores de Restrição Antivirais , Ubiquitina-Proteína Ligases
3.
Small ; : e2309086, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321834

RESUMO

Ferroptosis therapy, which uses ferroptosis inducers to produce lethal lipid peroxides and induce tumor cell death, is considered a promising cancer treatment strategy. However, challenges remain regarding how to increase the accumulation of reactive oxygen species (ROS) in the tumor microenvironment (TME) to enhance antitumor efficacy. In this study, a hyaluronic acid (HA) encapsulated hollow mesoporous manganese dioxide (H-MnO2 ) with double-shell nanostructure is designed to contain iron coordinated cyanine near-infrared dye IR783 (IR783-Fe) for synergistic ferroptosis photodynamic therapy against tumors. The nano photosensitizer IR783-Fe@MnO2 -HA, in which HA actively targets the CD44 receptor, subsequently dissociates and releases Fe3+ and IR783 in acidic TME. First, Fe3+ consumes glutathione to produce Fe2+ , which promotes the Fenton reaction in cells to produce hydroxyl free radicals (·OH) and induce ferroptosis of tumor cells. In addition, MnO2 catalyzes the production of O2 from H2 O2 and enhances the production of singlet oxygen (1 O2 ) by IR783 under laser irradiation, thus increasing the production and accumulation of ROS to provide photodynamic therapy. The highly biocompatible IR783-Fe@MnO2 -HA nano-photosensitizers have exhibited tumor-targeting ability and efficient tumor inhibition in vivo due to the synergistic effect of photodynamic and ferroptosis antitumor therapies.

4.
Plant Biotechnol J ; 22(2): 347-362, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37795910

RESUMO

Plant defence against pathogens generally occurs at the expense of growth and yield. Uncoupling the inverse relationship between growth and defence is of great importance for crop breeding, while the underlying genes and regulatory mechanisms remain largely elusive. The exocytosis complex was shown to play an important role in the trafficking of receptor kinases (RKs) to the plasma membrane (PM). Here, we found a Cucumis sativus exocytosis subunit Exo70B (CsExo70B) regulates the abundance of both development and defence RKs at the PM to promote fruit elongation and disease resistance in cucumber. Knockout of CsExo70B resulted in shorter fruit and susceptibility to pathogens. Mechanistically, CsExo70B associates with the developmental RK CsERECTA, which promotes fruit longitudinal growth in cucumber, and contributes to its accumulation at the PM. On the other side, CsExo70B confers to the spectrum resistance to pathogens in cucumber via a similar regulatory module of defence RKs. Moreover, CsExo70B overexpression lines showed an increased fruit yield as well as disease resistance. Collectively, our work reveals a regulatory mechanism that CsExo70B promotes both fruit elongation and disease resistance by maintaining appropriate RK levels at the PM and thus provides a possible strategy for superior cucumber breeding with high yield and robust pathogen resistance.


Assuntos
Cucumis sativus , Cucumis sativus/genética , Frutas/metabolismo , Resistência à Doença/genética , Melhoramento Vegetal , Membrana Celular
5.
Opt Express ; 32(11): 20303-20315, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859144

RESUMO

Optical scatterometry, also referred to as optical critical dimension (OCD) metrology, is a widely used technique for characterizing nanostructures in semiconductor industry. As a model-based optical metrology, the measurement in optical scatterometry is not straightforward but involves solving a complicated inverse problem. So far, the methods for solving the inverse scattering problem, whether traditional or deep-learning-based, necessitate a predefined geometric model, but they are also constrained by this model with poor applicability. Here, we demonstrate a sketch-guided neural network (SGNN) for nanostructure reconstruction in optical scatterometry. By learning from training data based on the designed generic profile model, the neural network acquires not only scattering knowledge but also sketching techniques, that allows it to draw the profiles corresponding to the input optical signature, regardless of whether the sample structure is the same as the generic profile model or not. The accuracy and strong generalizability of proposed approach is validated by using a series of one-dimensional gratings. Experiments have also demonstrated that it is comparable to nonlinear regression methods and outperforms traditional deep learning methods. To our best knowledge, this is the first time that the concept of sketching has been introduced into deep learning for solving the inverse scattering problem. We believe that our method will provide a novel solution for semiconductor metrology, enabling fast and accurate reconstruction of nanostructures.

6.
J Exp Bot ; 75(1): 300-315, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37738614

RESUMO

Aliphatic glucosinolates are a large group of plant secondary metabolites characteristic of Brassicaceae, including the model plant Arabidopsis. The diverse and complex degradation products of aliphatic glucosinolates contribute to plant responses to herbivory, pathogen attack, and environmental stresses. Most of the biosynthesis genes in the aliphatic glucosinolate pathway have been cloned in Arabidopsis, and the research focus has recently shifted to the regulatory mechanisms controlling aliphatic glucosinolate accumulation. Up till now, more than 40 transcriptional regulators have been identified as regulating the aliphatic glucosinolate pathway, but many more novel regulators likely remain to be discovered based on research evidence over the past decade. In the current study, we took a systemic approach to functionally test 155 candidate transcription factors in Arabidopsis identified by yeast one-hybrid assay, and successfully validated at least 30 novel regulators that could significantly influence the accumulation of aliphatic glucosinolates in our experimental set-up. We also showed that the regulators of the aliphatic glucosinolate pathway have balanced positive and negative effects, and glucosinolate metabolism and plant development can be coordinated. Our work is the largest scale effort so far to validate transcriptional regulators of a plant secondary metabolism pathway, and provides new insights into how the highly diverse plant secondary metabolism is regulated at the transcriptional level.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Glucosinolatos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas
7.
Chemistry ; 30(17): e202303553, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38251274

RESUMO

Domino reaction of benzo[d]thiazole-2-methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P-=2,3,4,5-tetrakis(benzo[d]thiazol-2-yl)pyrrol-1-ide). The reaction process has been studied by assigning a series of intermediates based on time-dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent-convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1-(benzo[d]thiazol-2-yl)-N-(benzo[d]thiazol-2-ylmethyl)methanimine) and alkene C (1,2-bis(benzo[d]thiazol-2-yl)ethene) through oxidative self-condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C-C bonds and one C-N bond are formed through this six-step domino sequence. The corresponding organic skeleton (HP: 2,2',2'',2'''-(1H-pyrrole-2,3,4,5-tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4-diphenyl substituted analogue 2,2'-(3,4-diphenyl-1H-pyrrole-2,5-diyl)bis(benzo[d]thiazole) (DPB) (42 %).

8.
World J Urol ; 42(1): 235, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616238

RESUMO

OBJECTIVE: Few studies have investigated the impact of basal metabolic rate (BMR) on the development of urolithiasis, and the causal relationship is yet to be established. In this study, a two-sample Mendelian randomization (MR) analysis was utilized to identify the causal relationship between BMR and risk of urolithiasis. METHOD: Genetic instruments for BMR were drawn from a public genome-wide association study (GWAS). Summary dates on BMR and urolithiasis were obtained from a GWAS meta-analysis with sample sizes of 454,874 and 212,453, respectively. The inverse-variance weighted (IVW) method was provided as the main approach to estimate the causal relationship. The weighted-median method and the MR-Egger method were used as supplements to the IVW method. In addition, we conducted sensitivity analyses, including heterogeneity tests, pleiotropy tests and leave-one-out analysis, to assess the robustness of the outcomes. Furthermore, the funnel plot asymmetry was visually inspected to evaluate possible bias. RESULTS: The inverse-variance weighted data revealed that genetically predicted BMR significantly decreased the risk of urolithiasis [beta coefficient (beta): - 0.2366, odds ratio (OR): 0.7893, 95% confidence interval (CI) 0.6504-0.9579, p = 0.0166]. CONCLUSIONS: BMR has causal effects on urolithiasis in an MR study, and the risk of urolithiasis in patients with lower levels of BMR is higher.


Assuntos
Metabolismo Basal , Urolitíase , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Suplementos Nutricionais , Urolitíase/epidemiologia , Urolitíase/genética
9.
Soft Matter ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980096

RESUMO

In this paper, coacervates were formed with mixed micelles consisting of the anionic amino acid surfactant sodium lauroylsarcosinate (NLS) and amphoteric surfactant cocamidopropyl betaine (CAPB) in combination with cationic guar gum. Based on personal care formulation studies, coacervates were prepared by diluting a concentrated system with water to better suit the product application process. The phase behavior during dilution was revealed by turbidity, which was influenced by the mixed micelle ratio (X), salt concentration, and dilution ratio (R). Optical microscopy, cryo-SEM, SAXS and rotational rheometry were used to characterize the structure and properties of the coacervates, which strongly depended on the interaction strength between the polymer and micelles. Dominated by electrostatic interactions, the coacervates exhibited a dense porous structure with low water content and a high viscoelastic modulus, while weakened interactions resulted in a looser mesh internal structure with lower viscoelasticity, enhancing skin adsorption. These findings enhance our understanding of polymer-mixed micelle systems and offer practical strategies for controlling the properties of coacervates.

10.
Ecol Appl ; 34(1): e2887, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37210676

RESUMO

The invasive freshwater mussel Limnoperna fortunei (Dunker, 1857) has spread widely throughout Asia and South America, especially via interbasin water diversion and navigation. The middle route of the South-to-North Water Transfer Project (SNWTP), whose terminal is Beijing, has diverted more than 60 billion m3 of water from the Yangtze River Basin to Northern China since December 2014. L. fortunei has spread north to Beijing along the SNWTP, biofouling its channels and tunnels. To determine the status of L. fortunei's invasion in Beijing, we systematically inspected the water bodies receiving southern water, including all branches of the SNWTP, water treatment plants, lakes, reservoirs, and rivers. We measured the densities of adults and veligers of L. fortunei and conducted eDNA analyses of water samples. A generalized linear model and canonical correspondence analysis were adopted to investigate the correlations between environmental (e.g., water temperature, conductivity, pH, total nitrogen, and phosphorus) and biological (e.g., chlorophyll a, plankton density, and community composition) variables and the densities of adults and veligers of L. fortunei. Water temperature is the most important factor in determining the densities of D-shaped and pediveliger veligers, with explanatory variable contributions of 56.2% and 43.9%, respectively. The pH affects the densities of D-shaped, umbonated, and pediveliger veligers. The density of plantigrade veligers is negatively correlated with the conductivity and positively correlated with the concentration of chlorophyll a. Canonical correspondence analysis shows a weak correlation between the dominant phytoplankton taxa and the density of veligers. The densities of D-shaped, umbonated, and pediveliger veligers are positively correlated with the density of small phytoplankton (12.54 ± 4.33 µm), and the density of plantigrade veligers is positively correlated with the density of large (16.12 ± 5.96 µm) phytoplankton. The density of planktonic veligers is well correlated with local abiotic variables, and that of plantigrade veligers is less correlated with local abiotic variables. This finding implies that controlling early-stage veligers by altering water temperature, pH, and food size might effectively control the establishment of further L. fortunei colonies.


Assuntos
Mytilidae , Animais , Pequim , Clorofila A , Fitoplâncton , China , Lagos
11.
Bioorg Med Chem Lett ; 97: 129548, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37949379

RESUMO

GPR34 is a rhodopsin-like class G protein-coupled receptor (GPCR) that is involved in the development and progression of several diseases. Despite its importance, effective targeting strategies are lacking. We herein report a series of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid derivatives as a new class of GPR34 antagonists. Structure-activity relationship (SAR) studies led to the identification of the most potent compound, 5e, which displayed an IC50 value of 0.680 µM in the GloSensor cAMP assay and 0.059 µM in the Tango assay. 5e demonstrated low cytotoxicity and high selectivity in vitro, and it was able to dose-dependently inhibit Lysophosphatidylserine-induced ERK1/2 phosphorylation in CHO cells expressing GPR34. Furthermore, 5e displayed excellent efficacy in a mouse model of neuropathic pain without any apparent signs of toxicity. Collectively, this study has identified a promising compound, which shows great potential in the development of potent antagonists with a new chemical scaffold targeting GPR34.


Assuntos
Propionatos , Receptores de Lisofosfolipídeos , Animais , Cricetinae , Camundongos , Células CHO , Cricetulus , Receptores de Lisofosfolipídeos/antagonistas & inibidores , Receptores de Lisofosfolipídeos/química , Relação Estrutura-Atividade
12.
Mol Cell Probes ; 75: 101961, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579914

RESUMO

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.


Assuntos
Progressão da Doença , Neoplasias , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patologia , Regulação Neoplásica da Expressão Gênica , Animais , Transdução de Sinais
13.
Environ Res ; 241: 117653, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37980982

RESUMO

When confronted with wastewater that is characterized by complex composition, stable molecular structure, and high concentration, relying solely on photocatalytic technology proves inadequate in achieving satisfactory degradation results. Therefore, the integration of other highly efficient degradation techniques has emerged as a viable approach to address this challenge. Herein, a novel strategy was employed whereby the exfoliated g-C3N4 nanosheets (CNs) with exceptional photocatalytic performance, were intimately combined with porous rod-shaped cobalt ferrite (CFO) through a co-calcination process to form the composite CFO/CNs, which exhibited remarkable efficacy in the degradation of various organic pollutants through the combination of photocatalysis and Fenton-like process synergistically, exemplified by the representative case of tetracycline hydrochloride (TCH, 200 mL, 50 mg/L). Specifically, under 1 mM of peroxymonosulfate (PMS) and illumination conditions, 50 mg of 1CFO/9CNs achieved a TCH removal ratio of ∼90% after 60 min of treatment. Furthermore, this work comprehensively investigated the influence of various factors, including catalyst and PMS dosages, solution pH, and the presence of anions and humate, on the degradation efficiency of pollutants. Besides, quenching experiments and EPR tests confirmed the establishment of an S-scheme heterojunction between CNs and CFO, which facilitated the effective spatial separation of photoexcited charge carriers and preserved the potent redox potential of photogenerated electrons and holes. This work offers a valuable reference for the integration of photocatalysis with the PMS-based Fenton-like process.


Assuntos
Elétrons , Poluentes Ambientais , Porosidade , Iluminação
14.
Appl Opt ; 63(3): 721-729, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38294385

RESUMO

The infrared radiation properties of a satellite provide essential information for space target recognition. In this study, a 3D model of a satellite is obtained using a 3D reconstruction algorithm based on deep learning. The transient temperature field distribution on the target surface is simulated using the ANSYS finite element analysis method by integrating the solar zenith angle, the position of the satellite orbit, and the dynamic angle of the detector. The infrared radiation model is used to analyze the influence of target surface temperature, orbit position, and rotation angle on infrared radiation. The calculated results show that, under the set parameters, the temperature range of all targets is 280-380 K, and the temperature distribution determines the variation trend of radiation intensity. The variation trends of radiation intensity presented by different motion postures of satellites differ considerably. The radiation intensity variation of the triaxial stabilized attitude is relatively stable, whereas the radiation intensity of the spin-stabilized attitude exhibits remarkable periodic fluctuations. The periodic motion of satellite orbit leads to periodic fluctuations in infrared radiation. The obtained infrared radiation data provide support for target detection, tracking, recognition, and infrared detector parameter design.

15.
Blood Purif ; 53(6): 465-475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38228111

RESUMO

INTRODUCTION: The objective of this study was to examine the utility of protein kinase N1 (PKN1) as a biomarker of cardiac surgery-associated AKI (CSA-AKI). METHODS: A prospective cohort study of 110 adults undergoing on-pump cardiac surgery was conducted. The associations between post-operative PKN1 and CSA-AKI, AKI severity, need for renal replacement therapy (RRT), duration of AKI, length of ICU stay, and post-operative hospital stay were evaluated. RESULTS: Patients were categorized into three groups according to PKN1 tertiles. The incidence of CSA-AKI in the third tertile was 3.4-fold higher than that in the first. PKN1 was an independent risk factor for CSA-AKI. The discrimination of PKN1 to CSA-AKI assessed by ROC curve indicated that the AUC was 0.70, and the best cutoff was 5.025 ng/mL. This group (>5.025 ng/mL) was more likely to develop CSA-AKI (p < 0.001). The combined AUC of EuroSCORE, aortic cross-clamp time, and PKN1 was 0.82 (p < 0.001). A higher level of PKN1 was related to increased need for RRT, longer duration of AKI, and length of ICU and post-operative hospital stays. CONCLUSIONS: PKN1 could be a potential biomarker for the prediction of CSA-AKI. The combination of PKN1, EuroSCORE, and aortic cross-clamp time was likely to predict the occurrence of CSA-AKI.


Assuntos
Injúria Renal Aguda , Biomarcadores , Procedimentos Cirúrgicos Cardíacos , Proteína Quinase C , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Masculino , Estudos Prospectivos , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Idoso , Biomarcadores/sangue , Tempo de Internação , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico
16.
Eur Spine J ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858266

RESUMO

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. METHOD: 104 patients who underwent posterior osteotomy (Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. RESULT: The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO) after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0 ± 552.2 ml vs. 987.0 ± 638.5 ml, P = 0.038), time of operation (244.1 ± 63.0 min vs. 292.4 ± 87.6 min, P = 0.025) were favorable in Modified PSO group compared to control group. CONCLUSION: To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.

17.
Arch Pharm (Weinheim) ; 357(4): e2300591, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185750

RESUMO

In a continuous effort to develop Janus kinase 1 (JAK1)-selective inhibitors, a novel series of 4-amino-7H-pyrrolo[2,3-d]pyrimidine derivatives bearing the piperidinyl fragment were designed and synthesized according to a combination strategy. Through enzymatic assessments, the superior compound 12a with an IC50 value of 12.6 nM against JAK1 was identified and a 10.7-fold selectivity index over JAK2 was achieved. It was indicated that 12a displayed considerable effect in inhibiting the pro-inflammatory NO generated from lipopolysaccharide (LPS)-induced RAW264.7 macrophages, while on normal RAW264.7 cells, 12a exerted a weak cytotoxicity effect (IC50 = 143.3 µM). Furthermore, H&E stain assay demonstrated the conspicuous capacity of 12a to suppress CCl4-induced hepatic fibrosis levels in a dose-dependent manner in vivo. The binding model of 12a ideally reflects the excellent activity of JAK1 over the homologous kinase JAK2. Overall, 12a, a JAK1-selective inhibitor, exhibited potential for liver fibrosis and inflammatory diseases.


Assuntos
Inibidores de Proteínas Quinases , Pirimidinas , Relação Estrutura-Atividade , Pirimidinas/farmacologia , Pirimidinas/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química
18.
Toxicol Ind Health ; 40(5): 244-253, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518383

RESUMO

With the widespread use of manganese dioxide nanoparticles (nano MnO2), health hazards have also emerged. The inflammatory damage of brain tissues could result from nano MnO2, in which the underlying mechanism is still unclear. During this study, we aimed to investigate the role of ROS-mediated p38 MAPK pathway in nano MnO2-induced inflammatory response in BV2 microglial cells. The inflammatory injury model was established by treating BV2 cells with 2.5, 5.0, and 10.0 µg/mL nano MnO2 suspensions for 12 h. Then, the reactive oxygen species (ROS) scavenger (20 nM N-acetylcysteine, NAC) and the p38 MAPK pathway inhibitor (10 µM SB203580) were used to clarify the role of ROS and the p38 MAPK pathway in nano MnO2-induced inflammatory lesions in BV2 cells. The results indicated that nano MnO2 enhanced the expression of pro-inflammatory cytokines IL-1ß and TNF-α, elevated intracellular ROS levels and activated the p38 MAPK pathway in BV2 cells. Controlling intracellular ROS levels with NAC inhibited p38 MAPK pathway activation and attenuated the inflammatory response induced by nano MnO2. Furthermore, inhibition of the p38 MAPK pathway with SB203580 led to a decrease in the production of inflammatory factors (IL-1ß and TNF-α) in BV2 cells. In summary, nano MnO2 can induce inflammatory damage by increasing intracellular ROS levels and further activating the p38 MAPK pathway in BV2 microglial cells.


Assuntos
Compostos de Manganês , Microglia , Óxidos , Proteínas Quinases p38 Ativadas por Mitógeno , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Linhagem Celular
19.
Sensors (Basel) ; 24(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38544219

RESUMO

A metamaterial-inspired varactor-tuned antenna with frequency reconfigurability and pattern diversity is designed. Two different versions of a reconfigurable structure are integrated into a single antenna to excite two different orthogonal patterns, which realizes pattern diversity for MIMO applications. The outer annular Composite Right-/Left-Handed Transmission Line (CRLH-TL) works at the 1 mode and provides a broadside pattern, and the inner circular radiator loaded with split ring resonators (SRR) operates at the 0 mode and radiates an omnidirectional pattern, which realizes pattern diversity. By using surface-mounted varactors, the operating frequencies for the two radiation patterns can be tuned over a wide frequency range, from 1.7 GHz to 2.2 GHz, covering the 1.71-2.17 GHz LTE band, and a low mutual coupling between the two radiators is achieved. The antenna has also been prototyped. The measured results are in good agreement with the simulation results, verifying the proposed concept. The dual-mode MIMO system equipped with the proposed antenna elements is discussed within the context of a 3-D channel model, and it shows a superior array compactness and spectral efficiency (SE) performance compared to scenarios with single-mode elements.

20.
Nano Lett ; 23(12): 5467-5474, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37283534

RESUMO

Phase engineering of Pt-based intermetallic catalysts has been demonstrated as a promising strategy to optimize catalytic properties for a direct formic acid fuel cell. Pt-Bi intermetallic catalysts are attracting increasing interest due to their high catalytic activity, especially for inhibiting CO poisoning. However, the phase transformation and synthesis of intermetallic compounds usually occurring at high temperatures leads to a lack of control of the size and composition. Here, we report the synthesis of intermetallic ß-PtBi2 and γ-PtBi2 two-dimensional nanoplates with controlled sizes and compositions under mild conditions. The different phases of intermetallic PtBi2 can significantly affect the catalytic performance of the formic acid oxidation reaction (FAOR). The obtained ß-PtBi2 nanoplates exhibit an excellent mass activity of 1.1 ± 0.01 A mgPt-1 for the FAOR, which is 30-fold higher than that of commercial Pt/C catalysts. Moreover, intermetallic PtBi2 demonstrates high tolerance to CO poisoning, as confirmed by in situ infrared absorption spectroscopy.

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