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1.
Environ Res ; : 120006, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39299448

RESUMEN

The impacts of transgenic crops on soil microbiology and fertility are critical in determining their biosafety. While transgenic crops can alter soil microbes, their effects are often context-dependent; therefore, the ecological importance of these changes remains a topic of ongoing research. Using high-throughput sequencing, we investigated the effects of Bacillus thuringiensis (Bt) maize expressing the mcry1Ab and mcry2Ab genes (2A7) on soil nutrient dynamics, as well as the diversity and function of soil microbial communities, including bacteria and fungi, within different soil compartments. Our findings revealed a plant-shaped rhizosphere (RS) microbial community as a result of the selective recruitment of microorganisms from the surrounding environment. The transgene insertion had a significant impact on the RS niche, and several species eventually became associated with Z58 and 2A7 plants. For example, Neocosmospora rubicola fungal and Pantoea dispersa bacterial microorganisms were significantly decreased in the dual Bt-transgenic 2A7 rhizosphere but enriched in the Z58 rhizospheres. The activity of soil enzymes such as urease, invertase, and alkaline phosphatase was boosted by Bt-transgenic 2A7. LefSe analysis identified significant bacterial and fungal biomarker species that were responsible for the differential effects of Bt-transgenic 2A7 and control Z58 within rhizosphere soils. Mantel analysis further demonstrated that the root exudates of 2A7 altered nutrient-acquisition enzymes by influencing biomarker taxa. PICRUSt2 functional characterization revealed a significantly higher abundance of the phosphate-starvation-inducible protein in control Z58 than in Bt-transgenic 2A7. Furthermore, taxonomy, alpha (Shannon diversity), and beta diversity analyses all revealed niche-driven microbial profile differentiation. Niche partitioning also had a significant impact on N- and P-related COGs as well. Our findings suggests that Bt-transgenic 2A7 modulates rhizosphere microbial communities by affecting biomarker taxa and soil enzyme activity. These findings will promote sustainable agriculture practices by advancing our knowledge of the ecological effects of Bt crops on soil microbial communities.

2.
Light Sci Appl ; 13(1): 227, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227394

RESUMEN

In just over a decade, certified single-junction perovskite solar cells (PSCs) boast an impressive power conversion efficiency (PCE) of 26.1%. Such outstanding performance makes it highly viable for further development. Here, we have meticulously outlined challenges that arose during the industrialization of PSCs and proposed their corresponding solutions based on extensive research. We discussed the main challenges in this field including technological limitations, multi-scenario applications, sustainable development, etc. Mature photovoltaic solutions provide the perovskite community with invaluable insights for overcoming the challenges of industrialization. In the upcoming stages of PSCs advancement, it has become evident that addressing the challenges concerning long-term stability and sustainability is paramount. In this manner, we can facilitate a more effective integration of PSCs into our daily lives.

3.
Front Immunol ; 15: 1429946, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947318

RESUMEN

Introduction: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood. Methods: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics. Results: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells. Discussion: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.


Asunto(s)
Cigarrillo Electrónico a Vapor , Ferroptosis , Nicotina , Enfermedad Pulmonar Obstructiva Crónica , Animales , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/etiología , Ratones , Nicotina/efectos adversos , Nicotina/toxicidad , Nicotina/administración & dosificación , Cigarrillo Electrónico a Vapor/efectos adversos , Modelos Animales de Enfermedad , Citocinas/metabolismo , Ratones Endogámicos C57BL , Sistemas Electrónicos de Liberación de Nicotina , Masculino , Ratones Transgénicos
4.
Angew Chem Int Ed Engl ; : e202406705, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049163

RESUMEN

Solution-processed perovskite films generally possess small grain sizes and high density of grain boundaries, which intensify non-radiative recombination of carriers and limits the power conversion efficiency (PCE) of solar cells. In this study, we report the room-temperature ripening enabled by the synergy of hygroscopic salts and moisture in air for efficient hole-conductor-free printable mesoscopic perovskite solar cells (p-MPSCs). Treating perovskite films with proper hygroscopic salts in damp air induces obvious secondary recrystallization, which coarsens the grains size from hundreds of nanometers to several micrometers. It's proposed that the hygroscopic salt at grain boundaries could absorb moisture and form a complex which could not only serve as mass transfer channel but also assist in the dissolution of perovskite grains. This activates mass transfer between small grains and large grains since they possess different solubilities, and thus ripens the perovskite film. Consequently, p-MPSCs treated with the hygroscopic salt of NH4SCN show an improved power conversion efficiency of 20.13% from 17.94%, and maintain >98% of the initial efficiency under maximum power point tracking at 55±5°C for 350 hours.

5.
JCI Insight ; 9(15)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900587

RESUMEN

Pathological deposition and crosslinking of collagen type I by activated myofibroblasts drives progressive tissue fibrosis. Therapies that inhibit collagen synthesis have potential as antifibrotic agents. We identify the collagen chaperone cyclophilin B as a major cellular target of the natural product sanglifehrin A (SfA) using photoaffinity labeling and chemical proteomics. Mechanistically, SfA inhibits and induces the secretion of cyclophilin B from the endoplasmic reticulum (ER) and prevents TGF-ß1-activated myofibroblasts from synthesizing and secreting collagen type I in vitro, without inducing ER stress or affecting collagen type I mRNA transcription, myofibroblast migration, contractility, or TGF-ß1 signaling. In vivo, SfA induced cyclophilin B secretion in preclinical models of fibrosis, thereby inhibiting collagen synthesis from fibrotic fibroblasts and mitigating the development of lung and skin fibrosis in mice. Ex vivo, SfA induces cyclophilin B secretion and inhibits collagen type I secretion from fibrotic human lung fibroblasts and samples from patients with idiopathic pulmonary fibrosis (IPF). Taken together, we provide chemical, molecular, functional, and translational evidence for demonstrating direct antifibrotic activities of SfA in preclinical and human ex vivo fibrotic models. Our results identify the cellular target of SfA, the collagen chaperone cyclophilin B, as a mechanistic target for the treatment of organ fibrosis.


Asunto(s)
Ciclofilinas , Animales , Humanos , Ratones , Ciclofilinas/metabolismo , Ciclofilinas/antagonistas & inhibidores , Colágeno Tipo I/metabolismo , Fibrosis , Miofibroblastos/metabolismo , Miofibroblastos/efectos de los fármacos , Miofibroblastos/patología , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Modelos Animales de Enfermedad , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta1/metabolismo , Lactonas , Compuestos de Espiro
6.
Plants (Basel) ; 13(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38931104

RESUMEN

In this study, processing tomato (Solanum lycopersicum L.) 'Ligeer 87-5' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K+, Ca2+, and Mg2+ in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.

7.
Plant Cell Rep ; 43(6): 160, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38825616

RESUMEN

KEY MESSAGE: LeBAHD56 is preferentially expressed in tissues where shikonin and its derivatives are biosynthesized, and it confers shikonin acylation in vivo. Two WRKY transcriptional factors might regulate LeBAHD56's expression. Shikonin and its derivatives, found in the roots of Lithospermum erythrorhizon, have extensive application in the field of medicine, cosmetics, and other industries. Prior research has demonstrated that LeBAHD1(LeSAT1) is responsible for the biochemical process of shikonin acylation both in vitro and in vivo. However, with the exception of its documented in vitro biochemical function, there is no in vivo genetic evidence supporting the acylation function of the highly homologous gene of LeSAT1, LeBAHD56(LeSAT2), apart from its reported role. Here, we validated the critical acylation function of LeBAHD56 for shikonin using overexpression (OE) and CRISPR/Cas9-based knockout (KO) strategies. The results showed that the OE lines had a significantly higher ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than the control. In contrast, the KO lines had a significantly lower ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than controls. As for its detailed expression patterns, we found that LeBAHD56 is preferentially expressed in roots and callus cells, which are the biosynthesis sites for shikonin and its derivatives. In addition, we anticipated that a wide range of putative transcription factors might control its transcription and verified the direct binding of two crucial WRKY members to the LeBAHD56 promoter's W-box. Our results not only confirmed the in vivo function of LeBAHD56 in shikonin acylation, but also shed light on its transcriptional regulation.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Lithospermum , Naftoquinonas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Naftoquinonas/metabolismo , Lithospermum/genética , Lithospermum/metabolismo , Acilación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Sistemas CRISPR-Cas , Antraquinonas
8.
Front Cardiovasc Med ; 11: 1364376, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903969

RESUMEN

Left atrial appendage occluder (LAAO) dislodgement with embolization is a rare occurrence. If the LAAO migrates into the left atrium or ventricle, it can lead to acute heart failure or even death in a person, necessitating urgent surgical intervention. Currently, most cases of LAAO dislodgement are managed through open-heart surgery, while percutaneous retrieval of the LAAO has been reported only in a few cases with limited associated experience. This article reports a case of a patient in whom a migrated LACbes device was successfully retrieved using a catheter-based approach, demonstrating an innovative and minimally invasive treatment strategy.

9.
Hortic Res ; 11(5): uhae067, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38725460

RESUMEN

The low phosphorus (P) availability of acidic soils severely limits leguminous plant growth and productivity. Improving the soil P nutritional status can be achieved by increasing the P-content through P-fertilization or stimulating the mineralization of organic P via arbuscular mycorrhizal fungi (AMF) application; however, their corresponding impacts on plant and soil microbiome still remain to be explored. Here, we examined the effects of AMF-inoculation and P-fertilization on the growth of soybean with different P-efficiencies, as well as the composition of rhizo-microbiome in an acidic soil. The growth of recipient soybean NY-1001, which has a lower P-efficiency, was not significantly enhanced by AMF-inoculation or P-fertilization. However, the plant biomass of higher P-efficiency transgenic soybean PT6 was significantly increased by 46.74%-65.22% through AMF-inoculation. Although there was no discernible difference in plant biomass between PT6 and NY-1001 in the absence of AMF-inoculation and P-fertilization, PT6 had approximately 1.9-2.5 times the plant biomass of NY-1001 after AMF-inoculation. Therefore, the growth advantage of higher P-efficiency soybean was achieved through the assistance of AMF rather than P-fertilization in available P-deficient acidic soil. Most nitrogen (N)-fixing bacteria and some functional genes related to N-fixation were abundant in endospheric layer, as were the P-solubilizing Pseudomonas plecoglossicida, and annotated P-metabolism genes. These N-fixing and P-solubilizing bacteria were positive correlated with each other. Lastly, the two most abundant phytopathogenic fungi species accumulated in endospheric layer, they exhibited positive correlations with N-fixing bacteria, but displayed negative interactions with the majority of the other dominant non-pathogenic genera with potential antagonistic activity.

10.
PLoS One ; 19(4): e0301239, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635505

RESUMEN

The retinal pigment epithelium (RPE) is essential to maintain retinal function, and RPE cell death represents a key pathogenic stage in the progression of several blinding ocular diseases, including age-related macular degeneration (AMD). To identify pathways and compounds able to prevent RPE cell death, we developed a phenotypic screening pipeline utilizing a compound library and high-throughput screening compatible assays on the human RPE cell line, ARPE-19, in response to different disease relevant cytotoxic stimuli. We show that the metabolic by-product of the visual cycle all-trans-retinal (atRAL) induces RPE apoptosis, while the lipid peroxidation by-product 4-hydroxynonenal (4-HNE) promotes necrotic cell death. Using these distinct stimuli for screening, we identified agonists of the aryl hydrocarbon receptor (AhR) as a consensus target able to prevent both atRAL mediated apoptosis and 4-HNE-induced necrotic cell death. This works serves as a framework for future studies dedicated to screening for inhibitors of cell death, as well as support for the discussion of AhR agonism in RPE pathology.


Asunto(s)
Ensayos Analíticos de Alto Rendimiento , Epitelio Pigmentado de la Retina , Humanos , Epitelio Pigmentado de la Retina/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Apoptosis , Muerte Celular , Estrés Oxidativo
11.
Front Cardiovasc Med ; 11: 1363020, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486707

RESUMEN

Background: Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). Objective: To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. Methods: This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. Results: A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. Conclusion: In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

12.
Science ; 383(6688): 1198-1204, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38484055

RESUMEN

Printable mesoscopic perovskite solar cells (p-MPSCs) do not require the added hole-transport layer needed in traditional p-n junctions but have also exhibited lower power conversion efficiencies of about 19%. We performed device simulation and carrier dynamics analysis to design a p-MPSC with mesoporous layers of semiconducting titanium dioxide, insulating zirconium dioxide, and conducting carbon infiltrated with perovskite that enabled three-dimensional injection of photoexcited electrons into titanium dioxide for collection at a transparent conductor layer. Holes underwent long-distance diffusion toward the carbon back electrode, and this carrier separation reduced recombination at the back contact. Nonradiative recombination at the bulk titanium dioxide/perovskite interface was reduced by ammonium phosphate modification. The resulting p-MPSCs achieved a power conversion efficiency of 22.2% and maintained 97% of their initial efficiency after 750 hours of maximum power point tracking at 55 ± 5°C.

13.
Heliyon ; 10(5): e27261, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38468927

RESUMEN

To investigate the variation in the mechanical properties of clay under freeze-thaw cycles (FTCs), a series of experiments were conducted in the laboratory. Samples with different water contents and dry densities were subjected to FTCs ranging from 0 to 11 times. Then, cohesion, shear strength, internal friction angle and elastic modulus were obtained using triaxial test. The results show that with the increase in the number of FTCs, the shear strength, cohesion and elastic modulus decreased, while the internal friction angle increased slightly. However, the variation in the internal friction angle is not obvious, and the maximum increment is within 4°. The cohesion exhibited the most decrease after the first freeze-thaw action. Besides, under a same number of FTCs, four mechanical properties are significantly affected by water content and dry density. The shear strength, cohesion, elastic modulus and internal friction angle decrease with water content while increasing with dry density. Additionally, the elastic modulus is associated with confining pressure, which increases with confining pressure. This study provides evidence for the variation in mechanical properties of the soils subjected to FTCs and guides the design and construction of the cold regional engineering.

14.
Adv Mater ; 36(26): e2401319, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38531370

RESUMEN

Tailoring multifunctional additives for performing interfacial modifications, improving crystallization, and passivating defects is instrumental for the fabrication of efficient and stable perovskite solar cells (PSCs). Here, a Schiff base derivative, (chloromethylene) dimethyliminium chloride (CDCl), is introduced as an additive to modify the interface between the mesoporous TiO2 electron transport layer and the MAPbI3 light absorber during the annealing process. CDCl chemically links to TiO2 and MAPbI3 through coordination and hydrogen bonding, respectively, and results in the construction of fast electron extraction channels. CDCl also optimizes the energy-level alignment of the TiO2/MAPbI3 heterojunction and improves the pore-filling and crystallization of MAPbI3 in the mesoscopic scaffold, which inhibits nonradiative recombination and eliminates open-circuit voltage losses. As a result, an impressive power conversion efficiency of 19.74%, which is the best one ever reported, is obtained for printable carbon-based hole-conductor-free PSCs based on MAPbI3.

15.
Materials (Basel) ; 17(6)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38541600

RESUMEN

The physical and mechanical characteristics of seawater coral sand engineered cementitious composites (SCECC) were examined through uniaxial compression, three-point bending, and splitting tensile tests. The mechanical properties were scrutinized under varying fiber volume fraction conditions (V = 0%, 0.575%, 1.150%, 1.725%, and 2.300%). The experimental results indicated that the compressive strength, three-point bending strength, and split tensile strength of SCECC tended to increase with the rise in fiber volume fraction. The strengths attained their maximum values of 45.88, 12.56, and 3.03 MPa when the fiber volume fraction reached 2.300%. In the compression test, the compressive strength of the 7-day specimen can achieve more than 78.50% of that observed in the 28-day specimen. Three-point bending test has revealed that SCECC exhibits favorable strain-hardening and multi-crack cracking characteristics. Fracture patterns of SCECC exhibited variations corresponding to changes in fiber content, as illustrated by their load-deformation curves, the addition of PVA fibers can change the damage mode of cementitious composites from brittle to ductile. The fracture energy of SCECC further attests to its elevated toughness. This is due to the fact that the fibers delay the formation of microcracks and prevent crack expansion, thus significantly increasing the deformability of the material. By verifying its strength, deformability, fracture energy, and other key performance indicators, the feasibility of SCECC in coastal construction projects has been clarified. The successful development of SCECC provides an innovative and high-performance option for the construction of future island projects.

16.
Phytomedicine ; 126: 154894, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38377719

RESUMEN

BACKGROUND: Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents. Therefore, the demand for new targeted agents is critical. ß-tubulin isotype III (Tubb3) is a prognostic factor associated with cancer progression, including breast cancer, and targeting Tubb3 may lead to improve TNBC disease control. Shikonin, the active compound in the roots of Lithospermun erythrorhizon suppresses the growth of various types of tumors, and its efficacy can be improved by altering its chemical structure. PURPOSE: In this work, the anti-TNBC effect of a shikonin derivative (PMMB276) was investigated, and its mechanism was also investigated. STUDY DESIGN/METHODS: This study combines flow cytometry, immunofluorescence staining, immunoblotting, immunoprecipitation, siRNA silencing, and the iTRAQ proteomics assay to analyze the inhibition potential of PMMB276 on TNBC. In vivo study was performed, Balb/c female murine models with or without the small molecule treatments. RESULTS: Herein, we screened 300 in-house synthesized analogs of shikonin against TNBC and identified a novel small molecule, PMMB276; it suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase, suggesting that it could have a tumor suppressive role in TNBC. Tubb3 was identified as the target of PMMB276 using proteomic and biological activity analyses. Meanwhile, PMMB276 regulated microtubule dynamics in vitro by inducing microtubule depolymerization and it could act as a tubulin stabilizer by a different process than that of paclitaxel. Moreover, suppressing or inhibiting Tubb3 with PMMB276 reduced the growth of breast cancer in an experimental mouse model, indicating that Tubb3 plays a significant role in TNBC progression. CONCLUSION: The findings support the therapeutic potential of PMMB276, a Tubb3 inhibitor, as a treatment for TNBC. Our findings might serve as a foundation for the utilization of shikonin and its derivatives in the development of anti-TNBC.


Asunto(s)
Naftoquinonas , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Animales , Ratones , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/patología , Tubulina (Proteína) , Proteómica , Proliferación Celular
17.
Sensors (Basel) ; 24(2)2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38257420

RESUMEN

Hyperspectral images (HSIs) contain abundant spectral and spatial structural information, but they are inevitably contaminated by a variety of noises during data reception and transmission, leading to image quality degradation and subsequent application hindrance. Hence, removing mixed noise from hyperspectral images is an important step in improving the performance of subsequent image processing. It is a well-established fact that the data information of hyperspectral images can be effectively represented by a global spectral low-rank subspace due to the high redundancy and correlation (RAC) in the spatial and spectral domains. Taking advantage of this property, a new algorithm based on subspace representation and nonlocal low-rank tensor decomposition is proposed to filter the mixed noise of hyperspectral images. The algorithm first obtains the subspace representation of the hyperspectral image by utilizing the spectral low-rank property and obtains the orthogonal basis and representation coefficient image (RCI). Then, the representation coefficient image is grouped and denoised using tensor decomposition and wavelet decomposition, respectively, according to the spatial nonlocal self-similarity. Afterward, the orthogonal basis and denoised representation coefficient image are optimized using the alternating direction method of multipliers (ADMM). Finally, iterative regularization is used to update the image to obtain the final denoised hyperspectral image. Experiments on both simulated and real datasets demonstrate that the algorithm proposed in this paper is superior to related mainstream methods in both quantitative metrics and intuitive vision. Because it is denoising for image subspace, the time complexity is greatly reduced and is lower than related denoising algorithms in terms of computational cost.

18.
Small ; 20(16): e2307246, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38039499

RESUMEN

Perovskite solar cells (PSCs) with a booming high power conversion efficiency (PCE) are on their road toward industrialization. A proper design of the counter electrode (CE) with low cost, high conductivity, chemical stability, and good interface contact with the other functional layer atop the perovskite layer is vital for the overall performance of PSCs. Herein, the application of titanium nitride (TiN) is reported as a conductive medium for the printable CE in hole-conductor-free mesoscopic PSCs. TiN improves the conductivity of the CE and reduces the resistivity from 20 to 10 mΩ∙cm. TiN also improves the wettability of the CE with perovskite and enhances the back interface contact, which promotes charge collection. On the other hand, TiN is chemically stable during processing and undergoes no distinguishable chemical reaction with halide perovskite. Devices with TiN as the conductive media in the CE deliver a champion PCE of 19.01%. This work supplies a considerable choice for the CE design of PSCs toward industrial applications.

19.
Herz ; 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37923966

RESUMEN

BACKGROUND: Coronary computed tomography-derived fractional flow reserve (FFR-CT) assesses whether coronary artery lesions will result in myocardial ischemia. This study aimed to evaluate the predictive value of FFR-CT for cardiovascular events in patients with coronary artery disease (CAD). METHODS: Data were collected retrospectively from patients with CAD who underwent FFR-CT at our hospital from January 2020 to February 2022 (1-year average follow-up). Patients were divided into ischemic (FFR-CT ≤ 0.80) and non-ischemic (FFR-CT > 0.80) groups. The incidence of endpoint events (cardiac death, acute myocardial infarction, unplanned revascularization, unstable angina, and stable angina) was calculated. The FFR-CT value was correlated with endpoint events using Cox regression models and Kaplan-Meier survival curves. RESULTS: We recruited 134 patients (93 [69.4%] and 41 [30.6%] patients in the ischemic and non-ischemic groups, respectively). The ischemic group had a higher proportion of men, patients with type 2 diabetes and hypertension, and patients taking antiplatelet drugs and ß­blockers than did the non-ischemic group (all p < 0.05), whereas other parameters were comparable. Multivariate Cox regression analysis revealed no significant differences in cardiac death, acute myocardial infarction, unplanned revascularization, and unstable angina between the groups. The incidence of stable angina events (hazard ratio: 3.092, 95% confidence interval: 1.362-7.022, p = 0.007) was significantly higher in the ischemic group. Kaplan-Meier survival analysis revealed a significant difference in event-free survival for stable angina between the groups (p = 0.002). CONCLUSION: In patients with CAD, FFR-CT showed an independent predictive value for stable angina within 1 year of examination.

20.
Plants (Basel) ; 12(22)2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38005715

RESUMEN

The fatty acid desaturase (FAD) gene family plays a crucial regulatory role in the resistance process of plant biomembranes. To understand the role of FADs in tomato growth and development, this study identified and analyzed the tomato FAD gene family based on bioinformatics analysis methods. In this study, 26 SlFADs were unevenly distributed on 10 chromosomes. Phylogenetic analysis showed that the SlFAD gene family was divided into six branches, and the exon-intron composition and conserved motifs of SlFADs clustered in the same branch were quite conservative. Several hormone and stress response elements in the SlFAD promoter suggest that the expression of SlFAD members is subject to complex regulation; the construction of a tomato FAD protein interaction network found that SlFAD proteins have apparent synergistic effects with SPA and GPAT proteins. qRT-PCR verification results show that SlFAD participates in the expression of tomato root, stem, and leaf tissues; SlFAD8 is mainly highly expressed in leaves; SlFAD9 plays a vital role in response to salt stress; and SlFAB5 regulates all stages of fruit development under the action of exogenous hormones. In summary, this study provides a basis for a systematic understanding of the SlFAD gene family. It provides a theoretical basis for in-depth research on the functional characteristics of tomato SlFAD genes.

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