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1.
Cell ; 176(5): 1206-1221.e18, 2019 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-30773317

RESUMEN

Social behaviors, including behaviors directed toward young offspring, exhibit striking sex differences. Understanding how these sexually dimorphic behaviors are regulated at the level of circuits and transcriptomes will provide insights into neural mechanisms of sex-specific behaviors. Here, we uncover a sexually dimorphic role of the medial amygdala (MeA) in governing parental and infanticidal behaviors. Contrary to traditional views, activation of GABAergic neurons in the MeA promotes parental behavior in females, while activation of this population in males differentially promotes parental versus infanticidal behavior in an activity-level-dependent manner. Through single-cell transcriptomic analysis, we found that molecular sex differences in the MeA are specifically represented in GABAergic neurons. Collectively, these results establish crucial roles for the MeA as a key node in the neural circuitry underlying pup-directed behaviors and provide important insight into the connection between sex differences across transcriptomes, cells, and circuits in regulating sexually dimorphic behavior.


Asunto(s)
Complejo Nuclear Corticomedial/fisiología , Caracteres Sexuales , Conducta Sexual Animal/fisiología , Amígdala del Cerebelo/fisiología , Animales , Conducta Animal/fisiología , Complejo Nuclear Corticomedial/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , Responsabilidad Parental , Factores Sexuales , Conducta Social
2.
Small ; 20(5): e2305360, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37786291

RESUMEN

Thermoelectric (TE) building materials have the potential to revolutionize sustainable architecture by converting temperature differences into electrical energy. This study introduces geopolymeric TE materials enhanced with manganese dioxide (MnO2 ) as a modifying agent. Calorimetric experiments examine the impact of MnO2 on geopolymerization. Mechanical tests show that adding MnO2 (up to 5% by weight) improves the geopolymer composite's strength, achieving a peak compressive strength of 36.8 MPa. The Seebeck effect of the MnO2 -modified geopolymeric composite is also studied. The inclusion of MnO2 boosts the Seebeck coefficient of the geopolymer, reaching a notable 4273 µV C-1 at a 5% MnO2 dosage. This enhancement is attributed to an increase in the density of states (DOS) and a reduction in relaxation time. However, excessive MnO2 or high alkali levels may adversely affect the Seebeck coefficient by lengthening the relaxation time.

3.
Small ; 20(37): e2403198, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38738744

RESUMEN

Hydrogen bonding as a multifunctional tool has always influenced the structure of hybrid perovskites. Compared with the research on hydrogen bonding, the study of halogen-halogen interactions on the structure and properties of hybrid perovskites is still in its early stages. Herein, a polar bilayered hybrid perovskite (IEA)2FAPb2I7 (IEA+ is 2-iodoethyl-1-ammonium, FA is formamidinium) with iodine-substituted spacer is successfully constructed by changing the configuration of interlayer cations and regulating non-covalent interactions at the organic-inorganic interface, which shows a shorter interlayer spacing and higher density (ρ = 3.862 g cm-3). The generation of structure polarity in (IEA)2FAPb2I7 is caused by the synergistic effect of hydrogen bonding and halogen-halogen interactions. Especially, as the length of the carbon chain in organic cations decreases, the I---I interaction in the system gradually strengthens, which may be the main reason for the symmetry-breaking. Polarity-induced bulk photovoltaics (Voc = 1.0 V) and higher density endow the device based on (I-EA)2FAPb2I7 exhibit a high sensitivity of 175.6 µC Gy-1 cm-2 and an ultralow detection limit of 60.4 nGy s-1 at 0 V bias under X-ray irradiation. The results present a facile approach for designing polar multifunctional hybrid perovskites, also providing useful assistance for future research on halogen-halogen interactions.

4.
Nat Methods ; 18(10): 1223-1232, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34608315

RESUMEN

Spatial metabolomics can reveal intercellular heterogeneity and tissue organization. Here we report on the spatial single nuclear metabolomics (SEAM) method, a flexible platform combining high-spatial-resolution imaging mass spectrometry and a set of computational algorithms that can display multiscale and multicolor tissue tomography together with identification and clustering of single nuclei by their in situ metabolic fingerprints. We first applied SEAM to a range of wild-type mouse tissues, then delineated a consistent pattern of metabolic zonation in mouse liver. We further studied the spatial metabolic profile in the human fibrotic liver. We discovered subpopulations of hepatocytes with special metabolic features associated with their proximity to the fibrotic niche, and validated this finding by spatial transcriptomics with Geo-seq. These demonstrations highlighted SEAM's ability to explore the spatial metabolic profile and tissue histology at the single-cell level, leading to a deeper understanding of tissue metabolic organization.


Asunto(s)
Microambiente Celular , Biología Computacional/métodos , Cirrosis Hepática/metabolismo , Hígado/citología , Algoritmos , Animales , Hepatocitos/fisiología , Humanos , Hígado/fisiología , Metabolómica/métodos , Ratones , Reproducibilidad de los Resultados , Imagen Individual de Molécula , Transcriptoma
5.
FASEB J ; 37(1): e22716, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36527390

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a major health problem in Western countries and has become the most common cause of chronic liver disease. Although NAFLD is closely associated with obesity, inflammation, and insulin resistance, its pathogenesis remains unclear. The disease begins with excessive accumulation of triglycerides in the liver, which in turn leads to liver cell damage, steatosis, inflammation, and so on. P38γ is one of the four isoforms of P38 mitogen-activated protein kinases (P38 MAPKs) that contributes to inflammation in different diseases. In this research, we investigated the role of P38γ in NAFLD. In vivo, a NAFLD model was established by feeding C57BL/6J mice with a methionine- and choline-deficient (MCD) diet and adeno-associated virus (AAV9-shRNA-P38γ) was injected into C57BL/6J mice by tail vein for knockdown P38γ. The results indicated that the expression level of P38γ was upregulated in MCD-fed mice. Furthermore, the downregulation of P38γ significantly attenuated liver injury and lipid accumulation in mice. In vitro, mouse hepatocytes AML-12 were treated with free fatty acid (FFA). We found that P38γ was obviously increased in FFA-treated AML-12 cells, whereas knockdown of P38γ significantly suppressed lipid accumulation in FFA-treated AML-12 cells. Furthermore, P38γ regulated the Janus Kinase-Signal transducers and activators of transcription (JAK-STAT) signaling pathway. Inhibition of P38γ can inhibit the JAK-STAT signaling pathway, thereby inhibiting lipid accumulation in FFA-treated AML-12 cells. In conclusion, our results suggest that targeting P38γ contributes to the suppression of lipid accumulation in fatty liver disease.


Asunto(s)
Leucemia Mieloide Aguda , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Metabolismo de los Lípidos , Quinasas Janus/metabolismo , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Hígado/metabolismo , Transducción de Señal , Ácidos Grasos no Esterificados/metabolismo , Inflamación/metabolismo , Metionina/farmacología , Metionina/metabolismo , Leucemia Mieloide Aguda/metabolismo
6.
Int Microbiol ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805155

RESUMEN

Soluble phosphorus scarcity severely limits plant growth and crop yield. In this study, a strain of inorganic phosphorus-solubilizing bacteria, Lysinibacillus sphaericus, was isolated from rice rhizosphere soil. The available phosphorus content in liquid inorganic phosphorus identification medium and in L. sphaericus-inoculated soil increased from 204.28 mg/L to 1124.68 mg/L and from 4.75 mg/kg to 7.04 mg/kg, respectively. The pH decreased significantly from 6.87 to 6.14. Incubation with L. sphaericus significantly increased malic and succinic acid content in the liquid inorganic phosphorus identification medium and increased acid phosphatase and alkaline phosphatase activity in the soil. Inoculation with L. sphaericus significantly increased rice growth, chlorophyll a/b content, and photosynthesis by increasing the soluble phosphorus content in the rice rhizosphere soil under phosphorus-deficient conditions. Further analysis revealed that L. sphaericus improved soil phosphorus release by decreasing soil pH and promoting acid phosphatase and alkaline phosphatase activity. This study supports the production of microbial fertilizers to improve rice yield in phosphorus-deficient conditions.

7.
Phys Chem Chem Phys ; 26(12): 9096-9111, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38456310

RESUMEN

As one of the most promising energy storage devices, supercapacitors exhibit a higher power density than batteries. However, its low energy density usually requires high-performance electrode materials. Although the RuO2 material shows desirable properties, its high cost and toxicity significantly limit its application in supercapacitors. Recent developments demonstrated that Co-based materials have emerged as a promising alternative to RuO2 for supercapacitors due to their low cost, favorable redox reversibility and environmental friendliness. In this paper, the morphological control and performance engineering of Co-based materials are systematically reviewed. Firstly, the principle of supercapacitors is briefly introduced, and the characteristics and advantages of pseudocapacitors are emphasized. The special forms of cobalt-based materials are introduced, including 1D, 2D and 3D nanomaterials. After that, the ways to enhance the properties of cobalt-based materials are discussed, including adding conductive materials, constructing heterostructures and doping heteroatoms. Particularly, the influence of morphological control and modification methods on the electrochemical performances of materials is highlighted. Finally, the application prospect and development direction of Co-based materials are proposed.

8.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33597298

RESUMEN

Plant fertilization involves both an egg cell, which fuses with a sperm cell, and synergid cells, which guide pollen tubes for sperm cell delivery. Therefore, egg and synergid cell functional specifications are prerequisites for successful fertilization. However, how the egg and synergid cells, referred to as the "egg apparatus," derived from one mother cell develop into distinct cell types remains an unanswered question. In this report, we show that the final position of the nuclei in female gametophyte determines the cell fate of the egg apparatus. We established a live imaging system to visualize the dynamics of nuclear positioning and cell identity establishment in the female gametophyte. We observed that free nuclei should migrate to a specific position before egg apparatus specialization. Artificial changing in the nuclear position on disturbance of the actin cytoskeleton, either in vitro or in vivo, could reset the cell fate of the egg apparatus. We also found that nuclei of the same origin moved to different positions and then showed different cell identities, whereas nuclei of different origins moved to the same position showed the same cell identity, indicating that the final positions of the nuclei, rather than specific nucleus lineage, play critical roles in the egg apparatus specification. Furthermore, the active auxin level was higher in the egg cell than in synergid cells. Auxin transport inhibitor could decrease the auxin level in egg cells and impair egg cell identity, suggesting that directional and accurate auxin distribution likely acts as a positional cue for egg apparatus specialization.


Asunto(s)
Arabidopsis/citología , Óvulo Vegetal/citología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Diferenciación Celular , Núcleo Celular , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Células Vegetales/fisiología , Plantas Modificadas Genéticamente/citología
9.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38610517

RESUMEN

In the precise point positioning/real-time kinematic (PPP-RTK) technique, high-precision ionospheric delay correction information is an important prerequisite for rapid PPP convergence. The commonly used ionospheric modeling approaches in the PPP-RTKs only take the trend term of the ionospheric total electron content (TEC) variations into account. As a result, the residual ionospheric delay still affects the positioning solutions. In this study, we propose a two-step regional ionospheric modeling approach that involves combining a polynomial fitting model (PFM) and a Kriging interpolation (KI) model. In the first step, a polynomial fitting method is used to model the trend term of the ionospheric TEC variations. In the second step, a KI method is used to compensate for the residual term of the ionospheric TEC variations. Datasets collected from continuously operating reference stations (CORSs) in Hunan Province, China, are used to validate the PFM/KI method by comparing with a single PFM method and a combined PFM and inverse distance weighting interpolation (IDWI) method. The experimental results show that the two-step PFM/KI modeled ionospheric delay achieves an average root mean square (RMS) error of 1.8 cm, which is improved by about 48% and 23% when compared with the PFM and PFM/IDWI methods, respectively. Regarding the positioning performance, the PPP-RTK with the PFM/KI method takes an average of 1.8 min or 4.0 min to converge to a positioning accuracy of 1.3 cm or 2.5 cm in the horizontal and vertical directions, respectively. The convergence times are decreased by about 18% and 14% in the horizontal direction and 9% and 5% in the vertical direction over the PFM and the PFM/IDWI methods, respectively.

10.
J Infect Dis ; 228(8): 1060-1065, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37369369

RESUMEN

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has led to concerns that ancestral SARS-CoV-2-based vaccines may not be effective against newly emerging Omicron subvariants. The concept of "imprinted immunity" suggests that individuals vaccinated with ancestral virus-based vaccines may not develop effective immunity against newly emerging Omicron subvariants, such as BQ.1.1 and XBB.1. In this study, we investigated this possibility using hamsters. Although natural infection induced effective antiviral immunity, breakthrough infections in hamsters with BQ.1.1 and XBB.1 Omicron subvariants after receiving the 3-dose mRNA-lipid nanoparticle vaccine resulted in only faintly induced humoral immunity, supporting the possibility of imprinted immunity.


Asunto(s)
COVID-19 , Animales , Cricetinae , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Modelos Animales , Vacunas contra la COVID-19 , ARN Mensajero/genética , Vacunación , Anticuerpos Neutralizantes , Anticuerpos Antivirales
11.
Angew Chem Int Ed Engl ; 63(17): e202318800, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38443316

RESUMEN

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).


Asunto(s)
Nanopartículas , Ácidos Nucleicos , Colorantes Fluorescentes/química , Nanopartículas/química , Técnicas de Amplificación de Ácido Nucleico
12.
J Neurosci ; 42(8): 1587-1603, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-34987109

RESUMEN

Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENT Astrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurologic diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.


Asunto(s)
Astrocitos , Transcriptoma , Envejecimiento/patología , Animales , Astrocitos/fisiología , Femenino , Humanos , Masculino , Ratones , Sinapsis/fisiología , Microambiente Tumoral
13.
Anal Chem ; 95(31): 11706-11713, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37459193

RESUMEN

Cell membrane-associated RNA (mem-RNA) has been demonstrated to be cell-specific and disease-related and are considered as potential biomarkers for disease diagnostics, drug delivery, and cell screening. However, there is still a lack of methods specifically designed to extract mem-RNA from cells, limiting the discovery and applications of mem-RNA. In this study, we propose the first all-in-one solution for high-purity mem-RNA isolation based on two types of magnetic nanoparticles, named MREMB (Membrane-associated RNA Extraction based on Magnetic Beads), which achieved ten times enrichment of cell membrane components and over 90% recovery rate of RNA extraction. To demonstrate MREMB's potential in clinical research, we extracted and sequenced mem-RNA of typical breast cancer MCF-7, MDA-MB-231, and SKBR-3 cell lines and non-neoplastic breast epithelial cell MCF-10A. Compared to total RNA, sequencing results revealed that membrane/secreted protein-encoding mRNAs and long noncoding RNAs (lncRNAs) were enriched in the mem-RNA, some of which were significantly overexpressed in the three cancer cell lines, including extracellular matrix-related genes COL5A1 and lncRNA TALAM1. The results indicated that MREMB could enrich membrane/secreted protein-coding RNA and amplify the expression differences of related RNAs between cancer and non-neoplastic cells, promising for cancer biomarker discovery.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , ARN , Línea Celular , Mama/metabolismo , Membrana Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
14.
BMC Med ; 21(1): 487, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053181

RESUMEN

BACKGROUND: Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma. METHODS: We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed. RESULTS: After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76-0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected. CONCLUSIONS: This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.


Asunto(s)
Glioma , Herpes Zóster , Virosis , Humanos , Estudio de Asociación del Genoma Completo , Glioma/epidemiología , Glioma/genética , Análisis de la Aleatorización Mendeliana
15.
Mol Carcinog ; 62(11): 1630-1644, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37401867

RESUMEN

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

16.
Anticancer Drugs ; 34(5): 609-619, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36847041

RESUMEN

Lung adenocarcinoma is one of the most aggressive and rapidly fatal types of malignant lung tumor. Molecular docking and virtual screening were effectively and systematically used to identify specific targets in malignant tumors and screen potential drugs. Here, we screen perfect leading compounds from a medicate library (ZINC15 database) and analyze their properties (conveyance, absorption, metabolism, excretion, and harmless forecasts) with potential inhibition of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C. Further results demonstrated that ZINC000013817014 and ZINC000004098458 were screened out from the ZINC15 database and were identified to have a much better binding affinity and more favorable interaction vitality binding with KRAS G12C and less rat carcinogenicity, Ames mutagenicity, way better dissolvability in water and noninhibition with cytochrome P-450 2D6. Molecular dynamics simulation analysis indicated that the binding capacity of these two compounds and KRAS G12C, ZINC000013817014-KRAS G12C, and ZINC000004098458-KRAS G12C is stable in the natural environment. Our findings reveal that ZINC000013817014 and ZINC000004098458 were perfect leading compounds to be inhibitors binding with KRAS G12C, which were selected as safe drug candidates and a cornerstone for KRAS G12C-related medicine plan and improvement. What is more, we have conducted a Cell Counting Kit-8 to verify the exactly inhibitory effects of the two selected drugs on Lung adenocarcinoma. This study establishes a solid framework for systematic anticancer medication research and development.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Proteínas Proto-Oncogénicas p21(ras) , Simulación del Acoplamiento Molecular , Mutación , Neoplasias Pulmonares/tratamiento farmacológico , Oncogenes
17.
Eur Radiol ; 33(11): 7769-7778, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37171489

RESUMEN

OBJECTIVES: To determine whether dual-energy CT (DECT) can be used to accurately and reliably detect anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS: Participants with unilateral ACL rupture were prospectively enrolled, and the bilateral knees were scanned by DECT. A tissue-specific mapping algorithm was applied to improve the visualization of the ACLs. The 80-keV CT value, mixed-keV CT value, electron density (Rho), and effective atomic number (Zeff) were measured to quantitatively differentiate torn ACLs from normal ACLs. MRI and arthroscopy served as the reference standards. RESULTS: Fifty-one participants (mean age, 27.0 ± 8.7 years; 31 men) were enrolled. Intact and torn ACLs were explicitly differentiated on color-coded DECT images. The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs (p < 0.001). The optimal cutoff values were an 80-keV CT value of 61.8 HU, a mixed-keV CT value of 60.9 HU, and a Rho of 51.8 HU, with AUCs of 98.0% (95% CI: 97.0-98.9%), 99.2% (95% CI: 98.6-99.7%), and 99.8% (95% CI: 99.6-100.0%), respectively. Overall, DECT had almost perfect reliability and validity in detecting ACL integrity (sensitivity = 97.1% [95% CI: 88.1-99.8%]; specificity = 98.0% [95% CI: 89.5-99.9%]; PPV = 98.0% [95% CI: 93.0-99.8%]; NPV = 97.1% [95% CI: 91.7-99.4%]; accuracy = 97.5% [95% CI: 94.3-99.2%]). There was no evidence of a difference between MRI and DECT in the diagnostic performance (p > 0.99). CONCLUSION: DECT has excellent diagnostic accuracy and reliability in qualitatively and quantitatively diagnosing ACL rupture. CLINICAL RELEVANCE STATEMENT: DECT could validly and reliably diagnose ACL rupture using both qualitative and quantitative methods, which may become a promising substitute for MRI to evaluate the integrity of injured ACLs and the maturity of postoperative ACL autografts. KEY POINTS: • On color-coded DECT images, an uncolored ACL was a reliable sign for qualitatively diagnosing ACL rupture. • The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs, which contributed to the quantitative diagnosis of ACL rupture. • DECT had an almost perfect diagnostic performance for ACL rupture, and diagnostic capability was comparable between MRI and DECT.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/cirugía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Tomografía Computarizada por Rayos X/métodos
18.
BMC Pulm Med ; 23(1): 440, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957604

RESUMEN

BACKGROUND: The combination of the endocannabinoid system (ECS) and the type 2 cannabinoid receptor (CB2R) can activate various signal pathways, leading to distinct pathophysiological roles. This interaction has gained significant attention in recent research on fibrosis diseases. Focal adhesion kinase (FAK) plays a crucial role in regulating signals from growth factor receptors and Integrins. It is also involved in the transformation of fibroblasts into myofibroblasts. This study aims to investigate the impact of the CB2R agonist JWH133 on lung fibrosis and its potential to alleviate pulmonary fibrosis in mice through the FAK pathway. METHODS: The C57 mice were categorized into five groups: control, BLM, BLM + JWH133, BLM + JWH133 + NC, and BLM + JWH133 + FAK groups.JWH133 was administered to mice individually or in conjunction with the FAK vector. After 21 days, pathological changes in mouse lung tissues, inflammatory factor levels, hydroxyproline levels, and collagen contents were evaluated. Moreover, the levels of the FAK/ERK/S100A4 pathway-related proteins were measured. RESULTS: JWH133 treatment decreased inflammatory factor levels, attenuated pathological changes, and reduced extracellular matrix accumulation in the mouse model of bleomycin-induced pulmonary fibrosis; however, these effects were reversed by FAK. JWH133 attenuated fibrosis by regulating the FAK/ERK/S100A4 pathway. CONCLUSIONS: The results presented in this study show that JWH133 exerts a protective effect against pulmonary fibrosis by inhibiting the FAK/ERK/S100A4 pathway.Therefore, JWH133 holds promise as a potential therapeutic target for pulmonary fibrosis.


Asunto(s)
Agonistas de Receptores de Cannabinoides , Fibrosis Pulmonar , Transducción de Señal , Animales , Ratones , Bleomicina , Agonistas de Receptores de Cannabinoides/farmacología , Fibrosis , Proteína-Tirosina Quinasas de Adhesión Focal/antagonistas & inhibidores , Pulmón/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos
19.
Knee Surg Sports Traumatol Arthrosc ; 31(6): 2374-2385, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36138208

RESUMEN

PURPOSE: To evaluate the extent of tunnel widening after anterior cruciate ligament reconstruction (ACLR) using the all-inside technique and to establish its correlation with patient-reported clinical outcomes and femoral graft bending angle (GBA). METHODS: Tunnel widening was evaluated using computed tomography (CT)-based three-dimensional (3D) models, and the femoral GBA was directly measured on CT images using the Picture Archiving and Communication System (PACS) software. Clinical follow-up was routine procedure, and patient-reported clinical outcomes mainly included International Knee Documentation Committee (IKDC), Lysholm, and Knee Injury and Osteoarthritis Outcome Scores (KOOS) scores, and subjective knee stability assessment. RESULTS: Fifty-two patients received standard all-inside ACLR, with a median follow-up of 6 months. Reconstructed anterior cruciate ligaments (ACLs) were scanned during the first 3 days and 6 months after surgery. On both the femoral and tibial sides, bone tunnels were most significantly enlarged at the articular aperture segment; the femoral tunnel was 9.2 ± 1.3 mm postoperatively and was significantly enlarged by 32% to a mean tunnel diameter of 12.1 ± 2.0 mm at 6 months after surgery. Moreover, the extent of tunnel enlargement gradually decreased as the measured levels approached those of the bone cortex. The femoral tunnel center was shifted into the anterior and distal direction, and the tibial tunnel center was shifted into the posterior and lateral direction. Additionally, the mean femoral GBA was 105.9° ± 8.1° at the 6-month follow-up. Tunnel enlargement and GBA were not significantly correlated with patient-reported outcomes. CONCLUSIONS: Femoral and tibial tunnels were significantly greater and eccentrically shifted at the 6-month follow-up after all-side ACLR. However, the extent of tunnel widening does not markedly affect the short-term clinical outcomes. Meanwhile, the femoral GBA was not significantly correlated with femoral tunnel widening or patient-reported outcomes. Although the tunnel widening following all-inside ACLR was not associated with clinical outcomes, it potentially caused difficulties in revision ACLR. LEVEL OF EVIDENCE: Level IV.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Ligamento Cruzado Anterior/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Tibia/diagnóstico por imagen , Tibia/cirugía , Fémur/diagnóstico por imagen , Fémur/cirugía , Tomografía Computarizada por Rayos X/métodos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Hipertrofia/cirugía
20.
Int J Mol Sci ; 24(22)2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-38003278

RESUMEN

Common cutworm (CCW) is an omnivorous insect causing severe yield losses in soybean crops. The seedling-stage mini-tray identification system with the damaged leaf percentage (DLP) as an indicator was used to evaluate antixenosis against CCW in the Chinese soybean landrace population (CSLRP) under three environments. Using the innovative restricted two-stage multi-locus genome-wide association study procedure (RTM-GWAS), 86 DLP QTLs with 243 alleles (2-11/QTL) were identified, including 66 main-effect loci with 203 alleles and 57 QTL-environment interaction loci with 172 alleles. Among the main-effect loci, 12 large-contribution loci (R2 ≥ 1%) explained 25.45% of the phenotypic variation (PV), and 54 small-contribution loci (R2 < 1%) explained 16.55% of the PV. This indicates that the CSLRP can be characterized with a DLP QTL-allele system complex that has not been found before, except for a few individual QTLs without alleles involved. From the DLP QTL-allele matrix, the recombination potentials expressed in the 25th percentile of the DLP of all possible crosses were predicted to be reduced by 41.5% as the maximum improvement and 14.2% as the maximum transgression, indicating great breeding potential in the antixenosis of the CSLRP. From the QTLs, 62 candidate genes were annotated, which were involved in eight biological function categories as a gene network of the DLP. Changing from susceptible to moderate plus resistant varieties in the CSLRP, 26 QTLs had 32 alleles involved, in which 19 genes were annotated from 25 QTL-alleles, including eight increased negative alleles on seven loci and 11 decreased positive alleles on 11 loci, showing the major genetic constitution changes for the antixenosis enhancement at the seedling stage in the CSLRP.


Asunto(s)
Glycine max , Plantones , Animales , Spodoptera/genética , Alelos , Glycine max/genética , Plantones/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Fitomejoramiento , Fenotipo
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