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1.
J Colloid Interface Sci ; 670: 373-384, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38768550

RESUMEN

The fabrication of an S-scheme heterojunction demonstrates as an efficient strategy for achieving efficient charge separation and enhancing catalytic activity of piezocatalysts. In this study, a new S-scheme heterojunction was fabricated on the PbBiO2Br surface through the photo-deposition of NiO nanoparticles. It was then employed in the piezoelectric catalytic degradation of Rhodamine B (RhB). The results demonstrate that the NiO/PbBiO2Br composite exhibits efficient performance in piezocatalytic RhB degradation. The optimal sample is the NiO/PbBiO2Br synthesized after 2 h of irradiation, achieving a RhB degradation rate of 3.11 h-1, which is 12.4 times higher than that of pure PbBiO2Br. Simultaneous exposure to visible light and ultrasound further increases in the RhB degradation rate, reaching 4.60 h-1, highlighting the synergistic effect of light and piezoelectricity in the NiO/PbBiO2Br composite. A comprehensive exploration of the charge migration mechanism at the NiO/PbBiO2Br heterojunction was undertaken through electrochemical analyses, theoretical calculations, and in-situ X-ray photoelectron spectroscopy analysis. The outcomes reveal that p-type semiconductor NiO and n-type semiconductor PbBiO2Br possess matching band structures, establishing an S-scheme heterojunction structure at their interface. Under the combined effects of band bending, interface electric fields, and Coulomb attraction, electrons and holes migrate and accumulate on the conduction band of PbBiO2Br and valence band of NiO, respectively, thereby achieving effective spatial separation of charge carriers. The catalyst's synergistic photo-piezoelectric catalysis effect can be ascribed to its role in promoting the generation and separation of charge carriers under both light irradiation and the piezoelectric field. The results of this investigation offer valuable insights into the development and production of catalytic materials that exhibit outstanding performance through the synergy of piezocatalysis and photocatalysis.

2.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38539042

RESUMEN

OBJECTIVES: It has been demonstrated that neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy was safe and feasible referred to neoadjuvant chemotherapy for patients with non-small cell lung cancer undergoing sleeve lobectomy. Nevertheless, no survival data were reported in the previous researches. Therefore, we conducted this study to compare neoadjuvant ICI plus chemotherapy versus neoadjuvant chemotherapy followed by sleeve lobectomy for long-term survival outcomes. METHODS: Patients who underwent bronchial sleeve lobectomy following neoadjuvant ICI plus chemotherapy or neoadjuvant chemotherapy were retrospectively identified. Treatment response, perioperative outcomes, event-free survival and overall survival were compared between groups in the overall and the inverse probability of treatment weighting-adjusted cohort. RESULTS: A total of 139 patients with 39 lung cancer recurrence and 21 death were included. Among them, 83 (59.7%) and 56 (40.3%) patients received neoadjuvant chemotherapy and neoadjuvant ICI plus chemotherapy, respectively. After inverse probability of treatment weighting, more patients achieved complete pathological response in the neoadjuvant ICI plus chemotherapy group (6.0% vs 26.3%, P < 0.001). There was no significant difference regarding overall postoperative complication (23.8% vs 20.2%, P = 0.624) and specific complications (all P > 0.05). Patients receiving neoadjuvant ICI plus chemotherapy had favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.16-0.85, P = 0.020) and overall survival (hazard ratio 0.23, 95% confidence interval 0.06-0.80, P = 0.021). Multivariable analysis revealed that neoadjuvant ICI plus chemotherapy was an independent predictor for favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.15-0.86, P = 0.020, adjusted for clinical TNM stage). CONCLUSIONS: Neoadjuvant ICI plus chemotherapy was correlated with favourable long-term survival in patients with non-small cell lung cancer undergoing sleeve lobectomy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Terapia Neoadyuvante/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/etiología
3.
Clin Neurol Neurosurg ; 239: 108226, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38484603

RESUMEN

BACKGROUND AND PURPOSE: Studies on changes in the distal internal carotid artery based on high resolution magnetic resonance imaging (HRMRI) are scarce. Herein, we propose a histological classification system for patients with carotid artery pseudo-occlusion or occlusion based on preoperative HRMRI, for which we evaluated the feasibility and clinical implications. MATERIALS AND METHODS: From January 2017 to June 2021, 40 patients with Doppler ultrasound, CTA or MRA suggesting carotid artery occlusion were enrolled in this study. A new classification system based on HRMRI was established and subsequently verified by postoperative specimens. We recorded and analyzed patient characteristics, HRMRI data, recanalization rate, requirements of additional endovascular procedures, complications, and outcomes. RESULTS: Four histological classifications (type Ⅰ-Ⅳ) were identified. According to our classification system, 20 patients (50.00%) were type I, nine (22.50%) were type II, 7 (17.50%) were type III, and four (10.00%) were type Ⅳ. The success rate of recanalization was 88.89% (32/36) in type I-III patients. Four (44.44%) type Ⅱ patients and five (71.43%) type Ⅲ patients suffered from intraoperative dissection. CONCLUSION: Patients identified as types I (pseudo-occlusion) and II (thrombotic-occlusion) were able to be treated via hybrid revascularization with relatively low risk, while patients identified as type III (fibrous-occlusion) required more careful treatment. Recanalization is not suitable for patients identified as type Ⅳ. Our proposed classification system based on HRMRI data can be used as an adjunctive guide to predict the technical feasibility and success of revascularization via a hybrid technique.


Asunto(s)
Enfermedades de las Arterias Carótidas , Estenosis Carotídea , Trombosis , Humanos , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Estenosis Carotídea/complicaciones , Proyectos Piloto , Estudios de Factibilidad , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/cirugía , Arteria Carótida Interna/patología , Trombosis/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/cirugía , Enfermedades de las Arterias Carótidas/complicaciones , Imagen por Resonancia Magnética , Resultado del Tratamiento , Estudios Retrospectivos
4.
Langmuir ; 40(9): 4953-4965, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38377576

RESUMEN

The preparation of catalysts with heterojunction structures is a strategy to achieve efficient charge separation and high photocatalytic activity of photocatalysts. In this work, BiPO4/KNbO3 heterostructure photocatalysts were fabricated by a combination of hydrothermal and precipitation methods and subsequently employed in catalyzing N2-to-NH3 conversion and RhB degradation under light illumination. Morphological analysis revealed the effective dispersion of BiPO4 on KNbO3 nanocubes. Band structure analysis suggests that KNbO3 and BiPO4 exhibit suitable band potentials to form an S-scheme heterojunction. Under the joint action of the built-in electric field at the interface, energy band bending, and Coulomb attraction force, photogenerated electrons and holes with low redox performance are consumed, while those with high redox performance are effectively spatially separated. Consequently, the BiPO4/KNbO3 shows enhanced photocatalytic activity. The NH3 production rate of the optimal sample is 2.6 and 5.8 times higher than that of KNbO3 and BiPO4, respectively. The enhanced photoactivity of BiPO4/KNbO3 is also observed in the photocatalytic degradation of RhB. This study offers valuable insights for the design and preparation of S-scheme heterojunction photocatalysts.

5.
Quant Imaging Med Surg ; 14(2): 1994-2007, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38415155

RESUMEN

Background: Research has shown that carotid intima-media thickness (CIMT) could help to predict carotid plaque (CP) progression in patients with mild carotid stenosis. However, the debate continues as to the value of carotid intima thickness (CIT) in monitoring the development of CP in patients with severe carotid stenosis. This study sought to evaluate the relationships between CIT and the ultrasonic characteristics of CP and to analyze the value of CIT and the ultrasonic parameters of CP in assessing plaque vulnerability in advanced human carotid atherosclerosis. Methods: A total of 55 individuals who underwent carotid endarterectomy (CEA) were included in the study (mean age: 65±7 years; female: 9.1%). CIMT and CIT were examined at the common carotid artery (CCA). Plaque textural features, such as the gray-scale median (GSM), superb microvascular imaging (SMI) level, and total plaque area (TPA), were also identified. A Spearman correlation coefficient analysis was performed to examine the relationship between CIT and the ultrasonic parameters of CP. The CIT of various plaque types was compared. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic values of the ultrasound characteristics to evaluate CP vulnerability. Results: The mean CIT of all the participants was 0.382±0.095 mm, the mean CIT of the participants with stable plaques was 0.328±0.031 mm, and the mean CIT of participants with vulnerable plaques was 0.424±0.106 mm (P<0.001). CIT was associated with the SMI level (Spearman's correlation coefficient: r=0.392, P=0.005), TPA (Spearman's correlation coefficient: r=0.337, P=0.012). Patients with thicker CIT had larger lipid cores, higher levels of plaque vulnerability, and more intraplaque hemorrhages (IPHs). The areas under the ROCs (AUCs) with 95% confidence interval (CI) for CIMT, CIT, the SMI level, the GSM, the TPA, and the combined model for identifying vulnerable plaques were 0.673 (0.533-0.793), 0.849 (0.727-0.932), 0.771 (0.629-0.879), 0.669 (0.529-0.790), 0.858 (0.738-0.938), and 0.949 (0.854-0.990), respectively. Conclusions: CIT was associated with both the histology and ultrasonic features of CP. CIT may be helpful in the detection of severe CP development.

6.
Acta Neurochir (Wien) ; 166(1): 2, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38200390

RESUMEN

BACKGROUND AND PURPOSE: Pipeline embolization device (PED) is widely used in intracranial aneurysms, and the scope of applications for the PED, which is frequently used to treat cerebral aneurysms, is also growing. It has some effect on branching vessels as a result of its inherent properties. The effects of PED on the complications rate and branching vessels blockage have not yet been thoroughly investigated. OBJECTIVE: We conducted a systematic review searching reports from multiple databases on PED use for intracranial aneurysms, and analyzed the influence of PED on the occlusion rate of different branching vessels, and the influence of the amount of PED on the occlusion rate of branching vessels by meta-analysis. METHODS: We searched the literature using PUBMED, Web of Science, and OVID databases until August 2023. Inclusion criteria were that the study used only PED, included at least 10 patients, and recorded branching vessels occlusion rates, mortality, and neurological complications. RESULTS: Nine studies were analyzed consisting of 706 patients with 986 side branches. The results of the meta-analysis showed that application of more than one PED did not significantly elevate the rate of branching vessels occlusion compared to application of one PED (OR = 0.70; 95% CI: 0.34 to 1.43; P = 0.33). In the comparison of branching vessels occlusion rates in the anterior circulation, the anterior cerebral artery (ACA) had a significantly higher occlusion rate compared to the ophthalmic artery (OphA) (OR = 6.54; 95% CI: 3.05 to 14.01; P < 0.01), ACA also had a higher occlusion rate compared to the anterior choroidal artery (AchA) (OR = 15.44; 95% CI: 4.11 to 57.94 P < 0.01), ACA versus posterior communicating artery (PcomA) occlusion rate difference was not statistically significant (OR = 2.58; 95% CI: 0.63 to 12.82; P = 0.17), OphA versus AchA occlusion rate difference was not statistically significant (OR = 2.56; 95% CI: 0.89 to 7.38; P = 0.08), and the occlusion rate was significantly higher for PcomA compared to AchA (OR = 7.22; 95% CI: 2.49 to 20.95; P < 0.01) and lower for OphA compared to PcomA (OR = 0.33; 95% CI: 0.19 to 0.55; P < 0.01). CONCLUSION: The meta-analysis shows that use of multiple PEDs did not significantly increase the occlusion rate of branching vessels, and the larger the diameter of branching vessels covered by PED, the higher the occlusion rate of branching vessels. However, the incidence of complications is low after branching vessels occlusion in anterior circulation, which is related to the collateral circulation compensation of the branching vessels.


Asunto(s)
Aneurisma Intracraneal , Enfermedades Vasculares , Humanos , Aneurisma Intracraneal/terapia , Circulación Colateral , Arteria Cerebral Anterior , Prótesis Vascular
7.
Heliyon ; 10(2): e23987, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38293421

RESUMEN

This paper presents a theoretical framework for the business decision-making process of the power generators as price takers when considering the participation of energy storage. The framework assesses rational valuation, optimal sales strategies, and hedging options for power plants with and without a gross sales constraint. The valuation and optimal sales strategy problems are analyzed using a risk-neutral pricing approach, dynamic programming principles, and the trinomial tree model suitable for the regime switching model. The formulation of a price risk hedging scheme flexible and widely used over-the-counter electricity derivative, the electricity contract for difference, as a tool for hedging electricity spot price risk. The minimum variance hedge ratio and its corresponding hedging efficiency formula are derived. In the section of numerical simulations, we first use the EM algorithm to calibrate the electricity spot model based on electricity spot price data of Nord Pool. Numerical simulations are then conducted on the operational decision-making of power generators under three different forms of energy storage. The results of the simulations provide a basis for power generators to evaluate the real-time value of power plants, to select optimal real-time power sales, and to determine the optimal timing of power plant transfer and storage methods.

8.
J Cell Biol ; 223(1)2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37955924

RESUMEN

The EGFR-RAS-ERK pathway is one of the most important signaling cascades in cell survival, growth, and proliferation. Aberrant activation of this pathway is a common mechanism in various cancers. Here, we report that CDK2 is a novel regulator of the ERK pathway via USP37 deubiquitinase (DUB). Mechanistically, CDK2 phosphorylates USP37, which is required for USP37 DUB activity. Further, USP37 deubiquitinates and stabilizes ERK1/2, thereby enhancing cancer cell proliferation. Thus, CDK2 is able to promote cell proliferation by activating USP37 and, in turn, stabilizing ERK1/2. Importantly, combined CDK1/2 and EGFR inhibitors have a synergetic anticancer effect through the downregulation of ERK1/2 stability and activity. Indeed, our patient-derived xenograft (PDX) results suggest that targeting both ERK1/2 stability and activity kills cancer cells more efficiently even at lower doses of these two inhibitors, which may reduce their associated side effects and indicate a potential new combination strategy for cancer therapy.


Asunto(s)
Sistema de Señalización de MAP Quinasas , Neoplasias , Transducción de Señal , Humanos , Proliferación Celular , Supervivencia Celular , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , Receptores ErbB/antagonistas & inhibidores , Animales , Neoplasias/tratamiento farmacológico
9.
Cell ; 187(2): 294-311.e21, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38128537

RESUMEN

Lactylation is a lactate-induced post-translational modification best known for its roles in epigenetic regulation. Herein, we demonstrate that MRE11, a crucial homologous recombination (HR) protein, is lactylated at K673 by the CBP acetyltransferase in response to DNA damage and dependent on ATM phosphorylation of the latter. MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and HR. Inhibition of CBP or LDH downregulated MRE11 lactylation, impaired HR, and enhanced chemosensitivity of tumor cells in patient-derived xenograft and organoid models. A cell-penetrating peptide that specifically blocks MRE11 lactylation inhibited HR and sensitized cancer cells to cisplatin and PARPi. These findings unveil lactylation as a key regulator of HR, providing fresh insights into the ways in which cellular metabolism is linked to DSB repair. They also imply that the Warburg effect can confer chemoresistance through enhancing HR and suggest a potential therapeutic strategy of targeting MRE11 lactylation to mitigate the effects.


Asunto(s)
Proteínas de Unión al ADN , Proteína Homóloga de MRE11 , Reparación del ADN por Recombinación , Humanos , ADN , Roturas del ADN de Doble Cadena , Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Epigénesis Genética , Recombinación Homóloga , Proteína Homóloga de MRE11/metabolismo , Ácido Láctico/metabolismo
10.
Nature ; 624(7992): 645-652, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38093014

RESUMEN

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.


Asunto(s)
Células Dendríticas , Complicaciones de la Diabetes , Diabetes Mellitus , Susceptibilidad a Enfermedades , Hiperglucemia , Pulmón , Virosis , Animales , Ratones , Acetilcoenzima A/metabolismo , Acetilación , Cromatina/genética , Cromatina/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Complicaciones de la Diabetes/inmunología , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/inmunología , Diabetes Mellitus/metabolismo , Glucosa/metabolismo , Histonas/metabolismo , Hiperglucemia/complicaciones , Hiperglucemia/inmunología , Hiperglucemia/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/virología , Linfocitos T/inmunología , Virosis/complicaciones , Virosis/inmunología , Virosis/mortalidad , Virus/inmunología , Modelos Animales de Enfermedad , Humanos
11.
New Phytol ; 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38095050

RESUMEN

The cell wall is the major interface for arbuscular mycorrhizal (AM) symbiosis. However, the roles of cell wall proteins and cell wall synthesis in AM symbiosis remain unclear. We reported that a novel wall-associated kinase 13 (GhWAK13) positively regulates AM symbiosis and negatively regulates Verticillium wilt resistance in cotton. GhWAK13 transcription was induced by AM symbiosis and Verticillium dahliae (VD) infection. GhWAK13 is located in the plasma membrane and expressed in the arbuscule-containing cortical cells of mycorrhizal cotton roots. GhWAK13 silencing inhibited AM colonization and repressed gene expression of the mycorrhizal pathway. Moreover, GhWAK13 silencing improved Verticillium wilt resistance and triggered the expression of immunity genes. Therefore, GhWAK13 is considered an immune suppressor required for AM symbiosis and disease resistance. GhWAK7A, a positive regulator of Verticillium wilt resistance, was upregulated in GhWAK13-silenced cotton plants. Silencing GhWAK7A improved AM symbiosis. Oligogalacturonides application also suppressed AM symbiosis. Finally, GhWAK13 negatively affected the cellulose content by regulating the transcription of cellulose synthase genes. The results of this study suggest that immunity suppresses AM symbiosis in cotton. GhWAK13 affects AM symbiosis by suppressing immune responses.

12.
Ultrason Sonochem ; 100: 106616, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37769589

RESUMEN

A novel heterojunction composite of CoOx/Bi4Ti3O12 was synthesized through a combination of molten salt and photodeposition methods. The optimal sample exhibited superior performance in the piezocatalytic degradation of methyl orange (MO) dye with a degradation rate of 1.09 h-1, which was 2.4 times higher than that of pristine Bi4Ti3O12. Various characterizations were conducted to reveal the fundamental nature accountable for the outstanding piezocatalytic performance of CoOx/Bi4Ti3O12. The investigation of the band structure indicated that the CoOx/Bi4Ti3O12 composite formed a type-I p-n heterojunction structure, with CoOx acting as a hole trapper to effectively separate and transfer piezogenerated carriers. Significantly, the MO degradation rate of the best CoOx/Bi4Ti3O12 sample further increased to 2.96 h-1 under combined ultrasonic vibration and simulated sunlight. The synergy between piezocatalysis and photocatalysis can be ascribed to the following factors. The photoexcitation process ensures the sufficient generation of charge carriers in the CoOx/Bi4Ti3O12, while the piezoelectric field within Bi4Ti3O12 promotes the separation of electron-hole pairs in the bulk phase. Furthermore, the heterojunction structure between Bi4Ti3O12 and CoOx significantly facilitates the surface separation of charge carriers. This increased involvement of free electrons and holes in the reaction leads to a remarkable enhancement in catalytic MO degradation. This work contributes to the understanding of the coupling mechanism between the piezoelectric effect and photocatalysis, and also provides a promising strategy for the development of efficient catalysts for wastewater treatment.

13.
Langmuir ; 39(37): 13267-13278, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37672746

RESUMEN

In this study, NaNbO3 microcubes were introduced during the preparation of Bi2O2CO3 nanosheets to construct a series of NaNbO3/Bi2O2CO3 heterojunctions with varying NaNbO3 content. Their photoactivities for N2 fixation were examined and compared. Results demonstrated that 7.5% NaNbO3/Bi2O2CO3 had the highest photoactivity. The NH3 production rate under simulated solar light is 453.1 µmol L-1 g-1 h-1, representing 2.0 and 3.8-fold increases compared to those of Bi2O2CO3 and NaNbO3, respectively. A comprehensive investigation encompassing the physical and chemical properties of the NaNbO3/Bi2O2CO3 photocatalyst was conducted. Bi2O2CO3 nanosheets were discovered to be distributed on the NaNbO3 microcubes surface. The addition of NaNbO3 exhibited nearly no effect on the photoabsorption performance and specific surface area of the Bi2O2CO3. However, the tight contact between NaNbO3 and Bi2O2CO3 and their appropriate band positions led to the formation of a heterojunction structure between them. The electron drift occurring in the interface region induces the creation of an internal electric field and energy band bending. This facilitates the transfer of photogenerated electrons and holes through an S-scheme mechanism, achieving efficient separation without compromising the redox performance. As a result, the NaNbO3/Bi2O2CO3 composite exhibits exceptional performance in the photocatalytic nitrogen fixation reaction. This study expands the application of S-scheme photocatalysts in the field of N2 reduction and provides insights into the preparation of efficient S-scheme photocatalysts.

14.
Eur J Pharmacol ; 958: 175981, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37579968

RESUMEN

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease characterized by myofibroblast proliferation and extracellular matrix deposition that has a high mortality rate and limited therapeutic options. Flavokawain A(FKA) is the major component of chalcone in kava extract. FKA has been reported to inhibit TGF-ß1-induced cardiomyocyte fibrosis by suppressing ROS production in A7r5 cells, but the role and mechanism of FKA in pulmonary fibrosis are unknown. In this study, we evaluated the effect of FKA on pulmonary fibrosis using an animal model of bleomycin-induced pulmonary fibrosis and showed that FKA alleviated the development of pulmonary fibrosis in a dose-dependent manner and improved lung function as well as collagen deposition and extracellular matrix accumulation in mice. In vitro studies showed that FKA inhibited myofibroblast activation and lung fibrosis progression by inhibiting TGF-ß1/Smad signaling in a dose-dependent manner. In addition, we identified CXCL12 as a potential target of FKA through target prediction. Molecular docking, CETSA(cellular thermal displacement assay) and silver staining assays further demonstrated that FKA could interact with CXCL12 and that FKA could inhibit CXCL12 dimerization in vitro. Further analysis revealed that FKA could inhibit fibroblast activation and reduce extracellular matrix (ECM) production and collagen deposition by blocking CXCL12/CXCR4 signaling, and knocking down CXCR4 expression could weaken the inhibitory effect of FKA on CXCL12/CXCR4 signal transduction. In conclusion, our study showed that FKA inhibited CXCL12/CXCR4 signaling by inhibiting CXCL12 dimerization, blocked the CXCL12/CXCR4 signaling pathway and inhibited the TGF-ß1-mediated signaling pathway to ameliorate pulmonary fibrosis, and FKA is a promising therapeutic agent for pulmonary fibrosis.

16.
Phytochemistry ; 214: 113802, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37506992

RESUMEN

Nine undescribed labdane diterpenoids (1-9) and one undescribed ent-halimane diterpenoid (10) were isolated from the aerial parts of Leonurus sibiricus, together with four known analogues (11-14) during our searching for naturally occurring antitumor agents. Their structures were established by detailed spectroscopic analyses and electronic circular dichroism analysis. Compound 4 possessed a rare 10-epi labdane scaffold. All compounds except 5 were evaluated for their inhibitory activities against interleukin (IL)-6-stimulated signal transducer and activator of transcription (STAT3) expression using a luciferase reporter assay. Compound 1 showed the most inhibitory effect with the IC50 value 20.31 µM. Compound 1 inhibited the activation of JAK2/STAT3 signal pathway through binding to Gln326 of STAT3 in CNE cells. The antiproliferative evaluation of compound 1 against CNE, CAL-27, A549 and PANC-1 cells demonstrated that CNE cells were the most sensitive to 1. Furthermore, compound 1 showed moderate efficacy in inhibiting cell migration, invasion, and epithelial-mesenchymal transition in CNE cells. In addition, compound 1 also promoted ferroptosis in CNE cells in a dose-dependent manner. These results suggest that compound 1 might be a potential candidate lead for treating nasopharyngeal carcinoma.


Asunto(s)
Diterpenos , Leonurus , Dicroismo Circular , Diterpenos/farmacología , Diterpenos/química , Leonurus/química , Estructura Molecular , Factor de Transcripción STAT3/antagonistas & inhibidores
17.
Nat Ecol Evol ; 7(7): 1131-1140, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37308704

RESUMEN

The amniotic egg with its complex fetal membranes was a key innovation in vertebrate evolution that enabled the great diversification of reptiles, birds and mammals. It is debated whether these fetal membranes evolved in eggs on land as an adaptation to the terrestrial environment or to control antagonistic fetal-maternal interaction in association with extended embryo retention (EER). Here we report an oviparous choristodere from the Lower Cretaceous period of northeast China. The ossification sequence of the embryo confirms that choristoderes are basal archosauromorphs. The discovery of oviparity in this assumed viviparous extinct clade, together with existing evidence, suggests that EER was the primitive reproductive mode in basal archosauromorphs. Phylogenetic comparative analyses on extant and extinct amniotes suggest that the first amniote displayed EER (including viviparity).


Asunto(s)
Lagartos , Animales , Filogenia , Viviparidad de Animales no Mamíferos , Reproducción , Mamíferos
18.
J Thorac Dis ; 15(4): 2012-2021, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197556

RESUMEN

Background: Orthotopic models of lung cancer have been widely utilized, and the purpose of this study was to demonstrate the viability of our proposed modified modeling approach. Methods: A total of 50 female BALB/c mice were implanted with 1×1×1 mm fragments of a tumor sample into the left lung lobe. After 2 months of observation, the mice were humanely euthanized through CO2 inhalation. The macroscopic specimens were photographed, and the most representative neoplastic lesions were collected for histological analysis. Small-animal positron emission tomography/computed tomography (PET/CT) scans were conducted on 6 randomly selected mice. Results: Local tumor formation, ipsilateral thoracic tissue infiltration, the contralateral chest wall, right lung metastases, and distant kidney metastases were observed in these models. Overall, the tumor development and metastasis rates were 60.86% (28/46) and 57.14% (16/28), respectively. The 3 mice that had a small-animal PET/CT scan developed a local tumor, but no distant metastases were observed. Conclusions: This modified method was deemed reliable, reproducible, minimally invasive, straightforward, and comprehensible; it might serve as the foundation for developing patient-derived orthotopic xenografts of lung cancer.

19.
Inorg Chem ; 62(17): 6833-6842, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37067429

RESUMEN

Solar-driven hydrogen (H2) generation from seawater exhibits great economic value in addressing the urgent energy shortage yet faces challenges from the severe salt-deactivation effect, which could result in the consumption of photoinduced charges and decomposition of catalysts. Herein, a triptycene-based polymer was coated on the surface of a CdxZn1-xS nanorod to form a core-shell heterojunction (TCP@CZS) by using the in situ Suzuki reaction for photocatalytic H2 production from water/seawater splitting. The introduction of TCP can provide a large surface area, enrich the active site, and boost charge transfer for the proton reduction reaction. Benefiting from it, optimal TCP@CZS indicated a H2 evolution rate of 93.88 mmol h-1 g-1 with Na2S/Na2SO3 in natural seawater under simulated solar light irradiation, which was 2.2 and 1.1 times higher than that of pure Cd0.6Zn0.4S and that in pure water, respectively. Besides, the apparent quantum efficiency (AQE) of TCP@CZS-3 under 420 nm light irradiation was 22.6% in seawater. This work highlights the feasibility of the triptycene-based porous organic polymer as an efficient catalyst for solar energy conversion in seawater.

20.
Curr Opin Microbiol ; 73: 102287, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36868081

RESUMEN

Caloric restriction (CR) and related time-restricted diets have been popularized as means of preventing metabolic disease while improving general well-being. However, evidence as to their long-term efficacy, adverse effects, and mechanisms of activity remains incompletely understood. The gut microbiota is modulated by such dietary approaches, yet causal evidence to its possible downstream impacts on host metabolism remains elusive. Herein, we discuss the positive and adverse influences of restrictive dietary interventions on gut microbiota composition and function, and their collective impacts on host health and disease risk. We highlight known mechanisms of microbiota influences on the host, such as modulation of bioactive metabolites, while discussing challenges in achieving mechanistic dietary-microbiota insights, including interindividual variability in dietary responses as well as other methodological and conceptual challenges. In all, causally understanding the impact of CR approaches on the gut microbiota may enable to better decode their overall influences on human physiology and disease.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Humanos , Restricción Calórica , Dieta
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