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1.
Neural Regen Res ; 20(1): 265-276, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767491

RESUMO

JOURNAL/nrgr/04.03/01300535-202501000-00034/figure1/v/2024-05-14T021156Z/r/image-tiff Certain amino acids changes in the human Na+/K+-ATPase pump, ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1), cause Charcot-Marie-Tooth disease type 2 (CMT2) disease and refractory seizures. To develop in vivo models to study the role of Na+/K+-ATPase in these diseases, we modified the Drosophila gene homolog, Atpα, to mimic the human ATP1A1 gene mutations that cause CMT2. Mutations located within the helical linker region of human ATP1A1 (I592T, A597T, P600T, and D601F) were simultaneously introduced into endogenous DrosophilaAtpα by CRISPR/Cas9-mediated genome editing, generating the AtpαTTTF model. In addition, the same strategy was used to generate the corresponding single point mutations in flies (AtpαI571T, AtpαA576T, AtpαP579T, and AtpαD580F). Moreover, a deletion mutation (Atpαmut) that causes premature termination of translation was generated as a positive control. Of these alleles, we found two that could be maintained as homozygotes (AtpαI571T and AtpαP579T). Three alleles (AtpαA576T, AtpαP579 and AtpαD580F) can form heterozygotes with the Atpαmut allele. We found that the Atpα allele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila. Flies heterozygous for AtpαTTTF mutations have motor performance defects, a reduced lifespan, seizures, and an abnormal neuronal morphology. These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

2.
Cell Rep ; 43(7): 114444, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38990723

RESUMO

The emergence of novel traits is often preceded by a potentiation phase, when all the genetic components necessary for producing the trait are assembled. However, elucidating these potentiating factors is challenging. We have previously shown that an anthocyanin-activating R2R3-MYB, STRIPY, triggers the emergence of a distinct foliar pigmentation pattern in the monkeyflower Mimulus verbenaceus. Here, using forward and reverse genetics approaches, we identify three potentiating factors that pattern STRIPY expression: MvHY5, a master regulator of light signaling that activates STRIPY and is expressed throughout the leaf, and two leaf developmental regulators, MvALOG1 and MvTCP5, that are expressed in opposing gradients along the leaf proximodistal axis and negatively regulate STRIPY. These results provide strong empirical evidence that phenotypic novelties can be potentiated through incorporation into preexisting genetic regulatory networks and highlight the importance of positional information in patterning the novel foliar stripe.

3.
ACS Appl Bio Mater ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38986048

RESUMO

Marine biofouling directly affects the performance and efficiency of uranium (U(VI)) extraction from seawater. Compared to traditional chemical methods, natural plant extracts are generally biodegradable and nontoxic, making them an environmentally friendly alternative to synthetic chemicals in solving the marine biofouling problem. The effectiveness of natural antibacterial plants (i.e., pine needle, peppermint, Acorus gramineus Soland, Cacumen platycladi, and wormwood) in solving the marine biofouling problem was evaluated in this work. Experimental results showed that natural antibacterial plants could kill Vibrio alginolyticus in solution and effectively solve the marine biofouling problem of U(VI) extraction. To improve the adsorption capacity of natural plants for U(VI) in seawater, poly(vinylphosphonic acid) (PVPA) was modified on natural antibacterial plant surfaces by irradiation grafting technology. PVPA and natural antibacterial plants work as active sites and base materials for the U(VI) extraction material, respectively. The recovery performance of PVPA/pine needle for U(VI) was preliminarily studied. Results show that the adsorption of U(VI) on PVPA/pine needle follows pseudo-second-order and Langmuir models, and the maximum adsorption capacity is 111 mg/g at 298 K and pH 8.2.

4.
Chemistry ; : e202402023, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39032086

RESUMO

This study presents the design, synthesis, and comprehensive characterization of a novel series of D-π-A type malononitrile-derived chromophores, BTC-1 to BTC-4. Combining various spectroscopic techniques, nonlinear Z-scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (µ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and ICT collectively dictate the nonlinear optical properties of the compounds. Notably, BTC-1 exhibits an exceptional nonlinear absorption coefficient ß value (2 × 10-8 m W-1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high-performance organic NLO materials with potential applications in advanced photonic devices.

5.
Se Pu ; 42(6): 581-589, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38845519

RESUMO

Oils and fats are commonly used in the pharmaceutical industry as solvents, emulsifiers, wetting agents, and dispersants, and are an important category of pharmaceutical excipients. Fatty acids with unique compositions are important components of oil pharmaceutical excipients. The Chinese Pharmacopoeia provides clear descriptions of the fatty acid types and limits suitable for individual oil pharmaceutical excipient. An unqualified fatty acid composition or content may indicate adulteration or deterioration. The fatty acid composition, as a key indicator for the identification and adulteration evaluation of oil pharmaceutical excipients, can directly affect the quality and safety of oil pharmaceutical excipients and preparations. Gas chromatography is the most widely used technique for fatty acid analysis, but it generally requires derivatization, which affects quantitative accuracy. Supercritical fluid chromatography (SFC), an environmentally friendly technique with excellent separation capability, offers an efficient method for detecting fatty acids without derivatization. Unlike other chromatographic methods, SFC does not use nonvolatile solvents (e. g., water) as the mobile phase, rendering it compatible with an evaporative light-scattering detector (ELSD) for enhanced detection sensitivity. However, the fatty acids in oil pharmaceutical excipients exist in the free and bound forms, and the low content of free fatty acids in these oil pharmaceutical excipients not only poses challenges for their detection but also complicates the determination of characteristic fatty acid compositions and contents. Moreover, the compositions and ratios of fatty acids are influenced by environmental factors, leading to interconversion between their two forms. In this context, saponification provides a simpler and faster alternative to derivatization. Saponification degrades oils and fats by utilizing the reaction between esters and an alkaline solution, ultimately releasing the corresponding fatty acids. Because this method is more cost effective than derivatization, it is a suitable pretreatment method for the detection of fatty acids in oil pharmaceutical excipients using the SFC-ELSD approach. In this study, we employed SFC-ELSD to simultaneously determine six fatty acids, namely, myristic acid, palmitic acid, stearic acid, arachidic acid, docosanoic acid, and lignoceric acid, in oil pharmaceutical excipients. Saponification of the oil pharmaceutical excipients using sodium hydroxide methanol solution effectively avoided the bias in the determination of fatty acid species and contents caused by the interconversion of fatty acids and esters. The separation of the six fatty acids was achieved within 12 min, with good linearity within their respective mass concentration ranges. The limits of detection and quantification were 5-10 mg/L and 10-25 mg/L, respectively, and the spiked recoveries were 80.93%-111.66%. The method proved to be sensitive, reproducible, and stable, adequately meeting requirements for the analysis of fatty acids in oil pharmaceutical excipients. Finally, the analytical method was successfully applied to the determination of six fatty acids in five types of oil pharmaceutical excipients, namely, corn oil, soybean oil, coconut oil, olive oil, and peanut oil. It can be combined with principal component analysis to accurately differentiate different types of oil pharmaceutical excipients, providing technical support for the rapid identification and quality control of oil pharmaceutical excipients. Thus, the proposed method may potentially be applied to the analysis of complex systems adulterated with oil pharmaceutical excipients.


Assuntos
Cromatografia com Fluido Supercrítico , Excipientes , Ácidos Graxos , Ácidos Graxos/análise , Ácidos Graxos/química , Cromatografia com Fluido Supercrítico/métodos , Excipientes/análise , Excipientes/química , Espalhamento de Radiação , Luz , Óleos/química , Óleos/análise
6.
Int J Biol Macromol ; 271(Pt 1): 132198, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821789

RESUMO

To address the issue of bisphenol A (BPA) contamination in wastewater, a novel hydrogel, sodium alginate/cellulose nanofibrils/ZIF-8 composite hydrogel (SCZC), was synthesized for efficient BPA removal. The SCZC exhibited an exceptional adsorption capacity of 1696 mg/g, aligning well with both Langmuir and pseudo-second-order models. Furthermore, it exhibited remarkable regeneration properties, maintaining 89.1 % of its adsorption capacity even after undergoing five adsorption-desorption cycles. The synthesized SCZC also acted as a fluorescent sensor for detecting BPA, employing dynamic quenching and offering linear detection ranges of 10-100 mg/L and 0.2-1.0 µg/L, with a low detection limit of 0.06 µg/L. Analysis of adsorption and detection mechanisms revealed that SCZC's exceptional performance could be attributed to the three-dimensional (3D) porous structure formed by sodium alginate and cellulose nanofibrils. Economic analysis indicated that SCZC, in comparison to commercially activated carbon, was relatively inexpensive. This study introduces a novel approach for designing and preparing a sodium alginate-based hydrogel incorporating metal-organic frameworks, offering simultaneous BPA detection and removal capabilities.


Assuntos
Alginatos , Compostos Benzidrílicos , Celulose , Hidrogéis , Nanofibras , Fenóis , Poluentes Químicos da Água , Alginatos/química , Fenóis/análise , Fenóis/química , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/química , Celulose/química , Adsorção , Nanofibras/química , Hidrogéis/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Estruturas Metalorgânicas/química
7.
Surg Endosc ; 38(7): 3520-3530, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38816620

RESUMO

BACKGROUND: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND. METHODS: We performed a systemic literature review of PubMed, Embase, and Web of Science databases. Perioperative parameters were extracted and pooled for analysis. This meta-analysis provided an analysis of heterogeneity and prediction intervals. RESULTS: Five studies were included: 567 patients divided between 266 robotic and 301 LPLND. Overall operation time was longer in the robotic group than laparoscopic group (difference in means = 67.11, 95% CI [30.80, 103.42], p < 0.001) but the difference in the pelvic lateral lymph dissection time was not statistically significant (difference in means = - 1.212, 95% CI [ - 11.594, 9.171], p = 0.819). There were fewer overall complications in the robotic than in the laparoscopic group (OR = 1.589, 95% CI [1.009, 2.503], p = 0.046), especially with respect to urinary retention (OR = 2.23, 95% CI [1.277, 3.894], p = 0.005). More pelvic lateral lymph nodes were harvested by robotic surgery than by laparoscopy (differences in means = - 1.992, 95% CI [ - 2.421, 1.563], p < 0.001). CONCLUSIONS: In this meta-analysis, robotic pelvic lateral lymph node dissection was associated with more pelvic lateral lymph nodes harvested and lower overall complications, especially urinary retention when compared to LPLND. Further studies are needed to reinforce these findings.


Assuntos
Laparoscopia , Excisão de Linfonodo , Pelve , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Excisão de Linfonodo/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
8.
Trends Genet ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704304

RESUMO

It has been well documented that mutations in coding DNA or cis-regulatory elements underlie natural phenotypic variation in many organisms. However, the development of sophisticated functional tools in recent years in a wide range of traditionally non-model systems have revealed many 'unusual suspects' in the molecular bases of phenotypic evolution, including upstream open reading frames (uORFs), cryptic splice sites, and small RNAs. Furthermore, large-scale genome sequencing, especially long-read sequencing, has identified a cornucopia of structural variation underlying phenotypic divergence and elucidated the composition of supergenes that control complex multi-trait polymorphisms. In this review article we highlight recent studies that demonstrate this great diversity of molecular mechanisms producing adaptive genetic variation and the panoply of evolutionary paths leading to the 'grandeur of life'.

9.
World J Hepatol ; 16(5): 809-821, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38818287

RESUMO

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124407, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38723466

RESUMO

Copper is one of the common among the heavy metal pollution in Chinese herbal medicine (CHM). So, it is essential to develop rapid and accurate testing method to quantify the Cu2+ content in CHM. Herein, we prepared a coordination-based near-infrared fluorescent probe (NRh6G-FA) by introducing a hemicyanine dye in rhodamine 6G scaffold. NRh6G-FA had a high sensitivity, anti-interference performance, fast response (within 60 s), visualization (from light yellow to green) for Cu2+ and excellent sensing performance for the detection of Cu2+ at low concentrations (LOD = 0.225 µM). The most likely mechanism was verified on the basis of Job's plot, ESI-HRMS and DFT calculations. NRh6G-FA could be successfully applied for the detection and "naked eye" recognition of Cu2+ in CHM samples. Moreover, NRh6G-FA was used to visualize Cu2+ in living MCF-7 cells by confocal fluorescence imaging.


Assuntos
Cobre , Medicamentos de Ervas Chinesas , Corantes Fluorescentes , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Cobre/análise , Humanos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Células MCF-7 , Rodaminas/química , Imagem Óptica , Espectrometria de Fluorescência/métodos , Limite de Detecção
11.
Asian J Androl ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38727211

RESUMO

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

12.
Angew Chem Int Ed Engl ; 63(28): e202405498, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38651652

RESUMO

Three new nitrides La3MN5 (M=Cr, Mn, and Mo) have been synthesized using a high pressure azide route. These are the first examples of ternary Cs3CoCl5-type nitrides, and show that this (MN4)NLa3 antiperovskite structure type may be used to stabilise high oxidation-state transition metals in tetrahedral molecular [MN4]n- nitridometallate anions. Magnetic measurements confirm that Cr and Mo are in the M6+ state, but the M=Mn phase has an anomalously small paramagnetic moment and large cell volume. Neutron powder diffraction data are fitted using an anion-excess La3MnN5.30 model (space group I4/mcm, a=6.81587(9) Šand c=11.22664(18) Šat 200 K) in which Mn is close to the +7 state. Excess-anion incorporation into Cs3CoCl5-type materials has not been previously reported, and this or other substitution mechanisms may enable many other high oxidation state transition metal nitrides to be prepared.

13.
Molecules ; 29(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675677

RESUMO

Graphene-like 2D nanomaterials, such as graphene, MXene, molybdenum disulfide, and boron nitride, present a promising avenue for eco-friendly flame retardants. Their inherent characteristics, including metal-like conductivity, high specific surface area, electron transport capacity, and solution processability, make them highly suitable for applications in both structural fire protection and fire alarm systems. This review offers an up-to-date exploration of advancements in flame retardant composites, utilizing pristine graphene-like nanosheets, versatile graphene-like nanosheets with multiple functions, and collaborative systems based on these nanomaterials. Moreover, graphene-like 2D nanomaterials exhibit considerable potential in the development of early fire alarm systems, enabling timely warnings. This review provides an overview of flame-retarding and fire-warning mechanisms, diverse multifunctional nanocomposites, and the evolving trends in the development of fire alarm systems anchored in graphene-like 2D nanomaterials and their derivatives. Ultimately, the existing challenges and prospective directions for the utilization of graphene-like 2D nanomaterials in flame retardant and fire-warning applications are put forward.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 568-576, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660868

RESUMO

OBJECTIVE: To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells (HSCs) after treated by 5-FU in mouse. METHODS: Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells (HSPCs) in bone marrow (BM), the proportion of T cells, B cells and myeloid cells (TBM) in peripheral blood (PB) and spleen, and the development of T cells in thymus. Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle, apoptosis and the proportion of HSPCs in BM. The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro. RESULTS: SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice. SIRT5 deletion increased proportion of HSPCs in BM. After 5-FU treatment, the proportion of HSCs in SIRT5 deletion mice was significant decreased (P < 0.05), the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase (P < 0.05), and the proportion of early apoptosis increased (P < 0.05). By monoclonal culture in vitro, the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly (P < 0.05). CONCLUSION: SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro. SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.


Assuntos
Fluoruracila , Células-Tronco Hematopoéticas , Sirtuínas , Animais , Camundongos , Apoptose , Células da Medula Óssea , Ciclo Celular , Proliferação de Células , Fluoruracila/farmacologia , Sirtuínas/genética , Baço/citologia , Linfócitos T , Timo/citologia
15.
Immunity ; 57(4): 859-875.e11, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38513665

RESUMO

At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.


Assuntos
Interleucina-23 , Periodontite , Humanos , Células Epiteliais , Inflamação , Receptor 5 Toll-Like/metabolismo
16.
Acta Pharmacol Sin ; 45(6): 1264-1275, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38438582

RESUMO

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.


Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Receptor Tirosina Quinase Axl , Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Camundongos Nus , Compostos Organofosforados , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas , Pirimidinas , Receptores Proteína Tirosina Quinases , Animais , Feminino , Camundongos , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos BALB C , Mutação , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Echocardiography ; 41(3): e15779, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477165

RESUMO

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective method for controlling the heart rate of paroxysmal atrial fibrillation (PAF). However, recurrence is trouble under the RFCA. To gain a deeper understanding of the risk factors for recurrence in patients, we created a nomogram model to provide clinicians with treatment recommendations. METHODS: A total of two hundred thirty-three patients with PAF treated with RFCA at Guizhou Medical University Hospital between January 2021 and December 2022 were consecutively included in this study, and after 1 year of follow-up coverage, 166 patients met the nadir inclusion criteria. Patients with AF were divided into an AF recurrence group and a non-recurrence group. The nomogram was constructed using univariate and multivariate logistic regression analyses. By calculating the area under the curve, we analyzed the predictive ability of the risk scores (AUC). In addition, the performance of the nomogram in terms of calibration, discrimination, and clinical utility was evaluated. RESULTS: At the 12-month follow-up, 48 patients (28.92%) experienced a recurrence of AF after RFCA, while 118 patients (71.08%) maintained a sinus rhythm. In addition to age, sex, and TRV, LAD, and TTPG were independent predictors of recurrence of RFCA. The c-index of the nomogram predicted AF recurrence with an accuracy of .723, showing good decision curves and a calibrated nomogram, as determined by internal validation using a bootstrap sample size of 1000. CONCLUSION: We created a nomogram based on multifactorial logistic regression analysis to estimate the probability of recurrence in patients with atrial fibrillation 1 year after catheter ablation. This plot can be utilized by clinicians to predict the likelihood of recurrence.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Ablação por Radiofrequência , Humanos , Resultado do Tratamento , Nomogramas , Valor Preditivo dos Testes , Fatores de Risco , Ablação por Cateter/métodos , Catéteres , Recidiva
18.
J Formos Med Assoc ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38553294

RESUMO

BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). CONCLUSIONS: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38334841

RESUMO

The process of myocardial hypertrophy in hypertension can lead to excessive activation of oxidative stress. Lipoamide (ALM) has significant antioxidant and anti-inflammatory effects. This study aimed to investigate the effects of ALM on hypertension-induced cardiac hypertrophy, as well as explore its underlying mechanisms. We evaluated the effects of ALM on spontaneously hypertensive rats and rat cardiomyocytes treated with Ang II. We found that ALM was not effective in lowering blood pressure in SHR, but it attenuated hypertension-mediated cardiac fibrosis, oxidative stress, inflammation, and hypertrophy in rats. After that, in cultured H9C2 cells stimulated with Ang II, ALM increased the expression of antioxidant proteins that were decreased in the Ang II group. ALM also alleviated cell hypertrophy and the accumulation of ROS, while LY294002 partially abrogated these effects. Collectively, these results demonstrate that ALM could alleviate oxidative stress in cardiac hypertrophy, potentially through the activation of the PI3K/Akt-mediated Nrf2 signaling pathway.

20.
J Phys Chem Lett ; 15(9): 2476-2484, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38407931

RESUMO

The organic-inorganic hybrid heterojunction is introduced for the first time to break through the performance bottleneck of BiVO4-based photodetectors. Through a facile solution process, a p-n heterojunction is established at the BiVO4/PEDOT:PSS interface, and the built-in electric field is designed to separate photogenerated charge carriers. The hybrid heterojunction outputs a significantly increased photocurrent, which is 24 000 times larger than that of the bare BiVO4 thin film. The photodetector shows a satisfactory performance with a responsivity (R) and specific detectivity (D*) of 107.8 mA/W and 4.13 × 1010 Jones at 482 nm illumination. In addition to the fast response speed (100 ms), the device also exhibits an impressive long-term stability with a negligible attenuation in photocurrent after more than 700 cycles. This work provides a novel strategy to suppress carrier recombination of BiVO4, and the coupling of metal oxides and organic semiconductors opens up a new avenue for fabricating high-performance photodetectors.

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