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Kinesin is a kind of motor protein, which interacts with microtubule filaments and regulates cellulose synthesis. Cotton fiber is a natural model for studying the cellular development and cellulose synthesis. Therefore, a systematic research of Kinesin gene family in cotton (Gossypium spp.) will be beneficial for both understanding the function of Kinesin protein and assisting the fiber improvement. Here, we aimed to identify the key Kinesin genes present in cotton by combining genome-wide expression profile data, association mapping, and public quantitative trait loci (QTLs) in upland cotton (Gossypium hirsutum L.). Results showed that 159 Kinesin genes, including 15 genes of the Kinesin-13 gene subfamily, were identified in upland cotton; of which 157 Kinesin genes can be traced back to the diploid ancestors, G. raimondii and G. arboreum. Using a combined analysis of public QTLs and genome-wide expression profile information, there were 29 QTLs co-localized together with 28 Kinesin genes in upland cotton, including 10 Kinesin-13 subfamily genes. Genome-wide expression profile data indicated that, among the 28 co-localized genes, seven Kinesin genes were predominantly expressed in fibers or ovules. By association mapping analysis, 30 Kinesin genes were significantly associated with three fiber traits, among which a Kinesin-13 gene, Ghir_A11G028430, was found to be associated with both cotton boll length and lint weight, and one Kinesin-7 gene, Ghir_D04G017880 (Gh_Kinesin7), was significantly associated with fiber strength. In addition, two missense mutations were identified in the motor domain of the Gh_Kinesin7 protein. Overall, the Kinesin gene family seemingly plays an important role in cotton fiber and boll development. The exploited Kinesin genes will be beneficial for the genetic improvement of fiber quality and yield.
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Gossypium , Cinesinas , Gossypium/genética , Cinesinas/genética , Sitios de Carácter Cuantitativo/genética , Fibra de Algodón , CelulosaRESUMEN
Kinesin is a kind of motor protein, which interacts with microtubule filaments and regulates cellulose synthesis. Cotton fiber is a natural model for studying the cellular development and cellulose synthesis. Therefore, a systematic research of kinesin gene family in cotton (Gossypium spp.) will be beneficial for both understanding the function of kinesin protein and assisting the fiber improvement. Here, we aimed to identify the key kinesin genes present in cotton by combining genome-wide expression profile data, association mapping, and public quantitative trait loci (QTLs) in upland cotton (G. hirsutum L.). Results showed that 159 kinesin genes, including 15 genes of the kinesin-13 gene subfamily, were identified in upland cotton; of which 157 kinesin genes can be traced back to the diploid ancestors, G. raimondii and G. arboreum. Using a combined analysis of public QTLs and genome-wide expression profile information, there were 29 QTLs co-localized together with 28 kinesin genes in upland cotton, including 10 kinesin-13 subfamily genes. Genome-wide expression profile data indicated that, among the 28 co-localized genes, seven kinesin genes were predominantly expressed in fibers or ovules. By association mapping analysis, 30 kinesin genes were significantly associated with three fiber traits, among which a kinesin-13 gene, Ghir_A11G028430, was found to be associated with both cotton boll length and lint weight, and one kinesin-7 gene, Ghir_D04G017880 (Gh_Kinesin7), was significantly associated with fiber strength. In addition, two missense mutations were identified in the motor domain of the Gh_Kinesin7 protein. Overall, the kinesin gene family seemingly plays an important role in cotton fiber and boll development. The exploited kinesin genes will be beneficial for the genetic improvement of fiber quality and yield.
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Gossypium , Cinesinas , Gossypium/genética , Cinesinas/genética , Fibra de Algodón , Sitios de Carácter Cuantitativo/genética , Fenotipo , CelulosaRESUMEN
Somatic cell totipotency in plant regeneration represents the forefront of the compelling scientific puzzles and one of the most challenging problems in biology. How somatic embryogenic competence is achieved in regeneration remains elusive. Here, we discover uncharacterized organelle-based embryogenic differentiation processes of intracellular acquisition and intercellular transformation, and demonstrate the underlying regulatory system of somatic embryogenesis-associated lipid transfer protein (SELTP) and its interactor calmodulin1 (CAM1) in cotton as the pioneer crop for biotechnology application. The synergistic CAM1 and SELTP exhibit consistent dynamical amyloplast-plasmodesmata (PD) localization patterns but show opposite functional effects. CAM1 inhibits the effect of SELTP to regulate embryogenic differentiation for plant regeneration. It is noteworthy that callus grafting assay reflects intercellular trafficking of CAM1 through PD for embryogenic transformation. This work originally provides insight into the mechanisms responsible for embryogenic competence acquisition and transformation mediated by the Ca2+/CAM1-SELTP regulatory pathway, suggesting a principle for plant regeneration and cell/genetic engineering.
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Proteínas Portadoras , Plantas , OrgánulosRESUMEN
Endoplasmic reticulum stress (ERS) plays an important role in regulating the reproductive process of female mammals, mainly involved in follicular atresia and corpus luteum regression. DNA damage induced transcript 3 (DDIT3) is a marker gene of ERS. The objectives of the present study were to clone and analyze the sequence and tissue expression characteristics of DDIT3 gene in female yaks. By reverse transcriptase-polymerase chain reaction (RT-PCR) strategy, we obtained full-length 507-bp DDIT3-cDNA, encoding for 168-aa protein. Yak DDIT3 exhibited highest and least identity with that of bison and horse, respectively. Real-time PCR analyses revealed that the expression level of DDIT3 gene in ovary was higher than that in heart, liver, kidney, spleen, lung, uterus and oviduct (p < 0.05). DDIT3 expression level in ovary and uterus during pregnancy was higher than that in follicular phase, luteal phase and fetus stage. DDIT3 was highly expressed in metaphase II oocytes and granulosa cells than that in germinal vesicle and metaphase I oocytes (p < 0.05), respectively. This is the first molecular characterization and expression patterns of DDIT3 gene in female yaks. These results indicated that the DDIT3 gene possibly plays an important role in regulating ovary function and pregnancy maintenance in yaks.
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Atresia Folicular , Ovario , Embarazo , Bovinos , Femenino , Animales , Caballos , Clonación Molecular , Ovario/metabolismo , Oocitos , Reacción en Cadena en Tiempo Real de la Polimerasa , MamíferosRESUMEN
Background: Diminished ovarian reserve (DOR) can lead to amenorrhea, infertility, and even the development of premature ovarian insufficiency, severely affecting the quality of life for women. Therefore, it is important to determine the main components of Tonifying Yang Formula, analyze the active substances and effective targets for treating DOR using Tonifying Yang Formula, and explore its potential mechanisms of action. Objective: The study is aim to determine the main components of Tonifying Yang Formula, analyze the active substances and effective targets for treating DOR using Tonifying Yang Formula, and explore its potential molecular mechanisms of action, providing important theoretical basis for clinical application. Methods: The main active components of Tonifying Yang Formula and their potential therapeutic targets for DOR were searched using the Chinese Medicine Systems Pharmacology Database and Analysis Platform, BATMAN-TCM, GeneCards, OMIM, and Uniprot databases. The protein-protein interaction network of shared targets between drugs and diseases was constructed using the STRING database. The shared targets of drugs and diseases were subjected to GO analysis and KEGG pathway enrichment analysis using the DAVID database. AutoDock Vina was used to perform molecular docking between the active substances and key targets of the drug to validate their interaction activities. Results: The key chemical components in the Tonifying Yang Formula for DOR treatment include quercetin, luteolin, beta-sitosterol, stigmasterol, and kaempferol. The 164 key targets for treating DOR with Tonifying Yang Formula included AKT1, TNF, JUN, TP53, IL6, IL1B, EGFR, VEGFA, INS, and CASP3, among others. GO enrichment analysis revealed that the Tonifying Yang Formula mainly regulates gene expression positively, negatively regulates the apoptotic process, and affects signal transduction. KEGG pathway enrichment analysis showed that Tonifying Yang Formula is mainly involved in cancer-related pathways, the AGE-RAGE signaling pathway in diabetic complications, prostate cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. Molecular docking results indicated that the core components of the Tonifying Yang Formula had higher docking energies and stable binding with targets such as AKT1, IL6, JUN, TNF, and TP53. This study selected the PI3K/AKT signaling pathway for validation. Through experimental research, we found that Tonifying Yang Formula could improve ovarian reserve function by activating the PI3K/AKT signaling pathway. Conclusions: The potential mechanism of Tonifying Yang Formula therapy for DOR may be related to the influence of Chinese herbal compounds on pathways such as AKT1, IL6, JUN, TNF, and TP53, regulating the proliferation and apoptosis of ovarian granulosa cells, maintaining the function of the ovarian corpus luteum, regulating the secretion of related hormones, and alleviating ovarian tissue inflammation.
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Objective: Our aim was to perform a meta-analysis to compare the therapeutic effects of compound Xuanju capsules combined with hormone therapy vs hormone therapy alone in polycystic ovary syndrome (PCOS)-related infertility. Methods: Electronic databases including PubMed, The Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP database were manually searched. The quality of included studies was evaluated based on Cochrane Systematic Review standards, and the valid data were extracted for meta-analysis using RevMan 5.3 software (Cochrane Review). Results: A total of 14 randomized controlled trials (RCTs) including 1249 patients were included in the study. Meta-analysis showed that patients in the compound Xuanju capsule + hormone therapy group had higher estradiol (E2) levels and overall rates of effective treatment than patients in the hormone therapy alone group. Moreover, they exhibited lower levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as lower Kupperman scores, than the hormone therapy alone group. Conclusions: The combination of compound Xuanju capsules and hormone therapy is more effective than hormone therapy alone in the treatment of PCOS-related infertility. However, the quality of current studies is low, and high-quality clinical trials are warranted.
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Medicamentos Herbarios Chinos , Infertilidad , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Cápsulas , Medicamentos Herbarios Chinos/uso terapéutico , Hormonas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Interleukin-9 (IL-9) plays important role in coronary artery disease (CAD). However, the exact relationship between them is not explored yet. Here, four tag SNPs covering IL9 (rs31563, rs2069868, rs2069870 and rs31564) were selected to conduct case-control association analyses in a total of 3704 individuals from Chinese Han population (1863 CAD vs 1841 control). Results showed that: first, rs2069868 was associated with CAD combined with hypertension (Padjâ¯=â¯0.027); second, IL9 haplotype (CGAT) was associated with CAD (Padjâ¯=â¯0.035), and the combination genotype of "rs31563_CC/rs31564_TT" would remarkably decrease the risk of CAD (Padjâ¯=â¯0.001); third, significant associations were found between rs2069870 and decreased LDL-c levels and decreased total cholesterol levels, and between rs31563 and increased HDL-c levels (Padjâ¯<â¯0.05). Therefore, we conclude that IL9 might play a causal role in CAD by interacted with CAD traditional risk factors, which might confer a new way to improve the prevention and treatment of CAD.
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Enfermedad de la Arteria Coronaria , Interleucina-9 , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Enfermedad de la Arteria Coronaria/genética , Etnicidad , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
As the gene pool is exposed to both strain on land resources and a lack of diversity in elite allotetraploid cotton, the acquisition and identification of novel alleles has taken on epic importance in facilitating cotton genetic improvement and functional genomics research. Ethyl methanesulfonate (EMS) is an excellent mutagen that induces genome-wide efficient mutations to activate the mutagenic potential of plants with many advantages. The present study established, determined and verified the experimental procedure suitable for EMS-based mutant library construction as the general reference guide in allotetraploid upland cotton. This optimized method and procedure are efficient, and abundant EMS mutant libraries (approximately 12 000) in allotetraploid cotton were successfully obtained. More than 20 mutant phenotypes were observed and screened, including phenotypes of the leaf, flower, fruit, fiber and plant architecture. Through the plants mutant library, high-throughput and high-resolution melting technology-based variation evaluation detected the EMS-induced site mutation. Additionally, based on overall genome-wide mutation analyses by re-sequencing and mutant library assessment, the examination results demonstrated the ideal quality of the cotton EMS-treated mutant library constructed in this study with appropriate high mutation density and saturated genome. What is more, the collection is composed of a broad repertoire of mutants, which is the valuable resource for basic genetic research and functional genomics underlying complex allotetraploid traits, as well as cotton breeding.
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Metanosulfonato de Etilo/metabolismo , Genoma de Planta/genética , Gossypium/genética , Mutágenos/metabolismo , Mutación/genética , Tetraploidía , Metanosulfonato de Etilo/farmacología , Fertilidad/genética , Biblioteca de Genes , Estudios de Asociación Genética , Estudio de Asociación del Genoma Completo , Células Germinativas de las Plantas , Germinación/genética , Gossypium/anatomía & histología , Mutágenos/farmacología , Polimorfismo de Nucleótido Simple/genética , Carácter Cuantitativo HeredableRESUMEN
The pharmacokinetic (PK) and potential effects of Emodin on liver cancer were systematically evaluated in this study. Both the intragastric administration (i.g.) and hypodermic injection (i.h.) of Emodin exhibited a strong absorption (absorption rate < 1 h) and elimination capacity (t1/2 ≈ 2 h). The tissue distribution of Emodin after i.h. was rapid and wide. The stability of Emodin in three species of liver microsomes wasrat >human> beagle dog. These PK data provided the basis for the subsequent animal experiments. In liver cancer patient tissues, the expression of vascular endothelial growth factor (VEGF)-induced signaling pathways, including phosphorylated VEGF receptor 2 (VEGFR2), AKT, and ERK1/2,were simultaneously elevated, but miR-34a expression was reduced and negatively correlated with SMAD2 and SMAD4. Emodin inhibited the expression of SMAD2/4 in HepG2 cells by inducing the miR-34a level. Subsequently, BALB/c nude mice received a daily subcutaneous injection of HepG2 cells with or without Emodin treatment (1 mg/kg or 10 mg/kg), and Emodin inhibited tumorigenesis and reduced the mortality rate in a dose-dependent manner. In vivo experiments showed that cell proliferation, migration, and invasion were promoted by VEGF or miR-34a signal treatment but were inhibited when combined with Emodin treatment. All these results demonstrated that Emodin inhibited tumorigenesis in liver cancer by simultaneously inhibiting the VEGFR2-AKT-ERK1/2signaling pathway and promoting a miR-34a-mediated signaling pathway.
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Antineoplásicos/uso terapéutico , Emodina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , MicroARNs/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Proteínas Sanguíneas/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Perros , Emodina/sangre , Emodina/farmacocinética , Emodina/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
In recent decades, non-fullerene acceptors (NFAs) are undergoing rapid development and emerging as a hot area in the field of organic solar cells. Among the high-performance non-fullerene acceptors, aromatic diimide-based electron acceptors remain to be highly promising systems. This review discusses the important progress of perylene diimide (PDI)-based polymers as non-fullerene acceptors in all-polymer solar cells (all-PSCs) since 2014. The relationship between structure and property, matching aspects between donors and acceptors, and device fabrications are unveiled from a synthetic chemist perspective.
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Meiosis is a critical biological process for reproduction and genetic variation in higher plants. Gene duplication is a prominent feature of plant genomic architecture. Meiosis and gene duplication are of fundamental importance in unraveling the nature of genetics and evolution. The ideas and findings in this letter demonstrate a highly significant connection between meiosis and gene duplication, bring together these two disparate fields of study and highlight the importance of meiosis for understanding the evolutionary success of flowering plants. These insights and opinions open a new area of investigation and point to a significant way to illustrate the impact of duplicated genes on meiosis and fitness in higher plants, as well as their ultimate evolutionary, ecological, and agronomic impacts in light of challenges that have arisen due to global climate change. This study addresses novel ideas and viewpoints in plant developmental genomics and evolution.
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Duplicación de Gen , Gossypium/citología , Gossypium/genética , Meiosis/genética , Flores/genética , Regulación de la Expresión Génica de las Plantas , Genes Duplicados , Células Germinativas de las Plantas/citología , Células Germinativas de las Plantas/metabolismo , Transducción de Señal/genéticaRESUMEN
Plant regeneration via somatic embryogenesis (SE) is a key step during genetic engineering. In the current study, integrated widely targeted metabolomics and RNA sequencing were performed to investigate the dynamic metabolic and transcriptional profiling of cotton SE. Our data revealed that a total of 581 metabolites were present in nonembryogenic staged calli (NEC), primary embryogenic calli (PEC), and initiation staged globular embryos (GE). Of the differentially accumulated metabolites (DAMs), nucleotides, and lipids were specifically accumulated during embryogenic differentiation, whereas flavones and hydroxycinnamoyl derivatives were accumulated during somatic embryo development. Additionally, metabolites related to purine metabolism were significantly enriched in PEC vs. NEC, whereas in GE vs. PEC, DAMs were remarkably associated with flavonoid biosynthesis. An association analysis of the metabolome and transcriptome data indicated that purine metabolism and flavonoid biosynthesis were co-mapped based on the Kyoto encyclopedia of genes and genomes (KEGG) database. Moreover, purine metabolism-related genes associated with signal recognition, transcription, stress, and lipid binding were significantly upregulated. Moreover, several classic somatic embryogenesis (SE) genes were highly correlated with their corresponding metabolites that were involved in purine metabolism and flavonoid biosynthesis. The current study identified a series of potential metabolites and corresponding genes responsible for SE transdifferentiation, which provides a valuable foundation for a deeper understanding of the regulatory mechanisms underlying cell totipotency at the molecular and biochemical levels.
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Flavonoides/metabolismo , Gossypium/metabolismo , Purinas/metabolismo , Transdiferenciación Celular , Regulación de la Expresión Génica de las Plantas/genética , Gossypium/genética , Metaboloma/genética , Metaboloma/fisiología , Transcriptoma/genéticaRESUMEN
BACKGROUND/AIMS: Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. METHODS: Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. RESULTS: With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. CONCLUSIONS: We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice.
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Diabetes Mellitus Tipo 1/patología , Cardiomiopatías Diabéticas/patología , Animales , Factor Natriurético Atrial/genética , Factor Natriurético Atrial/metabolismo , Glucemia/análisis , Peso Corporal , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Cardiomiopatías Diabéticas/complicaciones , Modelos Animales de Enfermedad , Ecocardiografía , Femenino , Corazón/diagnóstico por imagen , Frecuencia Cardíaca , Ventrículos Cardíacos/diagnóstico por imagen , Masculino , Ratones , Ratones Endogámicos C57BL , Miocardio/patología , Péptido Natriurético Encefálico/genética , Péptido Natriurético Encefálico/metabolismo , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Triplet materials have been employed to achieve high-performing organic solar cells (OSCs) by extending the exciton lifetime and diffusion distances, while the triplet non-fullerene acceptor materials have never been reported for bulk heterojunction OSCs. Herein, for the first time, three triplet molecular acceptors based on tellurophene with different degrees of ring fusing were designed and synthesized for OSCs. Significantly, these molecules have long exciton lifetime and diffusion lengths, leading to efficient power conversion efficiency (7.52 %), which is the highest value for tellurophene-based OSCs. The influence of the extent of ring fusing on molecular geometry and OSCs performance was investigated to show the power conversion efficiencies (PCEs) continuously increased along with increasing the extent of ring fusing.
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Anthropogenic activities exhibit intricate and significant relationships with atmospheric CO2 concentration. Dissecting the spatiotemporal patterns and potential drivers of their coupling coordination relationships from geospatial and temporal perspectives contributes to the benign coordinating development between the two. The coupling coordination degree (D) and types, and their potential influencing factors in China were explored using a coupling coordination model, emerging hotspot analysis, and Multiscale Geographically Weighted Regression model. Results revealed D was dominated by basic coordination in China with notable spatial disparities. Generally, D exhibited higher values in the eastern regions and lower values in the western regions divided by the Hu Line. Furthermore, Central and East China exhibited lower coordination degrees compared to other eastern regions. A total of 15 spatiotemporal dynamic patterns were identified across China. Hot spot patterns were concentrated in the eastern regions of the Hu Line, while cold spots were mainly observed in the western regions. The coupling coordination types exhibited a distinct pattern of "coordination in the east and incoherence in the west, divided by the Hu Line". Over time, there was a shift from lower-level to more benign coordinated types. Additionally, the D and coupling coordination types demonstrated significant spatial agglomeration characteristics, and intercity alliances and enhanced collaborations are essential for sustaining low-carbon improvements. The mechanisms and intensities of various factors on D exhibited spatiotemporal differences. The key drivers influencing coupling coordination types varied depending on the specific type. Additionally, the scales of these drivers affecting D changed over time. It is essential to consider natural and meteorological factors and their scaling effects when developing policies to enhance coupling coordination level. These results have significant implications for assessing the relationship between atmospheric CO2 and human activities and provide guidance for implementing effective low-carbon development policies.
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This study aims to investigate the effect and mechanism of dehydroepiandrosterone (DHEA) on diminished ovarian reserve (DOR) by modulating the AMPK-SIRT1 signaling and mitophagy in rats. Three-month-old female Sprague-Dawley (SD) rats were randomized and injected intraperitoneally with sesame oil as the control or deoxyvinylcyclohexene (VCD) to induce DOR. The VCD-injected rats were randomized and injected subcutaneously with vehicle as the model group or with DHEA for 21 days as the DHEA group. After being identified in proestrus, rat blood samples were collected to prepare serum samples, and their ovarian tissues were dissected. Compared with the controls, significantly lower serum estradiol (E2), anti-Müllerian hormone (AMH), and inhibin B (IHNB) and higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected in the model group (DOR rats). The model group of rats displayed an increase in follicular atresia and a decrease in ovarian volume and the number of growing follicles and corpus luteum, accompanied by increased frequency of oocyte apoptosis and reduced levels of mitochondrial function. Furthermore, significantly higher levels of the AMPK-SIRT1 signaling and mitophagy were observed in the ovaries of rats in the model group. In contrast, treatment with DHEA significantly ameliorated the hormone disorder and morphological changes in the ovaries, reduced the frequency of apoptotic oocytes, and improved mitochondrial function in the ovaries of DOR rats. Mechanistically, DHEA treatment significantly attenuated the AMPK-SIRT1 signaling and mitophagy in the ovaries of DOR rats. DHEA treatment reduced the severity of DOR and enhanced ovarian reserve function by attenuating the AMPK-SIRT1 signaling and mitophagy in the ovaries of rats.
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Proteínas Quinasas Activadas por AMP , Deshidroepiandrosterona , Mitofagia , Reserva Ovárica , Ratas Sprague-Dawley , Transducción de Señal , Sirtuina 1 , Animales , Femenino , Sirtuina 1/metabolismo , Reserva Ovárica/efectos de los fármacos , Deshidroepiandrosterona/farmacología , Transducción de Señal/efectos de los fármacos , Ratas , Mitofagia/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patologíaRESUMEN
PURPOSE: The evidence of apatinib plus immune checkpoint inhibitors (ICIs) and transarterial chemoembolization (TACE) for treating advanced hepatocellular carcinoma (HCC) is limited. This study aimed to compare the treatment efficacy and safety of apatinib plus ICIs and TACE with apatinib plus TACE in these patients. METHODS: This study retrospectively enrolled 90 patients with advanced HCC treated with apatinib plus TACE (A-TACE group, n = 52) or apatinib plus ICIs and TACE (IA-TACE group, n = 38). RESULTS: The objective response rate was numerically higher in IA-TACE group compared with A-TACE group without statistical significance (57.9% vs. 36.5%, P = 0.055). Disease control rate was not different between groups (86.8% vs. 76.9%, P = 0.248). Progression-free survival (PFS) was improved in IA-TACE group compared with A-TACE group (P = 0.018). The median PFS (95% confidence interval) was 12.5 (8.7-16.3) months in IA-TACE group and 8.5 (5.6-11.4) months in A-TACE group. Overall survival (OS) was also prolonged in IA-TACE group compared with A-TACE group (P = 0.007). The median OS (95% confidence interval) was 21.1 (15.8-26.4) months in IA-TACE group and 14.3 (11.5-17.1) months in A-TACE group. By multivariate Cox regression model, IA-TACE was independently associated with prolonged PFS (hazard ratio = 0.539, P = 0.038) and OS (hazard ratio = 0.447, P = 0.025). Most adverse events were not different between groups. Only the incidence of reactive cutaneous capillary endothelial proliferation was higher in IA-TACE group compared with A-TACE group (10.5% vs. 0.0%, P = 0.029). CONCLUSION: Apatinib plus ICIs and TACE may be an effective and safe treatment for patients with advanced HCC, but further large-scale studies are needed for verification.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Femenino , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Resultado del TratamientoRESUMEN
Covalent organic frameworks (COF) are porous crystalline polymers connected by covalent bonds. Due to their inherent high specific surface area, tunable pore size, and good stability, they have attracted extensive attention from researchers. In recent years, COF membrane materials developed rapidly, and a large amount of research work has been presented on the preparation methods, properties, and applications of COF membranes. This review focuses on the research on independent/pure continuous COF membranes. First, based on the membrane formation mechanism, COF membrane preparation methods are categorized into two main groups: bottom-up and top-down. Four methods are presented, namely, solvothermal, interfacial polymerization, steam-assisted conversion, and layer by layer. Then, the aperture, hydrophilicity/hydrophobicity and surface charge properties of COF membranes are summarized and outlined. According to the application directions of gas separation, water treatment, organic solvent nanofiltration, pervaporation and energy, the latest research results of COF membranes are presented. Finally, the challenges and future directions of COF membranes are summarized and an outlook provided. It is hoped that this work will inspire and motivate researchers in related fields.
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A collaborative manipulation strategy of proper heat treatment and self-customized hydrofluoroether-based electrolyte design has been proposed for boosting the sodium-ion storage kinetics of Prussian white cathodes. Improved monoclinic phase stability and electrolyte-cathode compatibility are responsible for an impressive discharge capacity of 148.4 mA h g-1 and excellent electrode reversibility.