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Composite visualization represents a widely embraced design that combines multiple visual representations to create an integrated view. However, the traditional approach of creating composite visualizations in immersive environments typically occurs asynchronously outside of the immersive space and is carried out by experienced experts. In this work, we aim to empower users to participate in the creation of composite visualization within immersive environments through embodied interactions. This could provide a flexible and fluid experience with immersive visualization and has the potential to facilitate understanding of the relationship between visualization views. We begin with developing a design space of embodied interactions to create various types of composite visualizations with the consideration of data relationships. Drawing inspiration from people's natural experience of manipulating physical objects, we design interactions based on the combination of 3D manipulations in immersive environments. Building upon the design space, we present a series of case studies showcasing the interaction to create different kinds of composite visualizations in virtual reality. Subsequently, we conduct a user study to evaluate the usability of the derived interaction techniques and user experience of creating composite visualizations through embodied interactions. We find that empowering users to participate in composite visualizations through embodied interactions enables them to flexibly leverage different visualization views for understanding and communicating the relationships between different views, which underscores the potential of several future application scenarios.

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INTRODUCTION: Through methodological quality assessment, this paper summarized the report quality and evidence level of systematic reviews (SRs)/meta-analyses (MAs) of acupuncture and its related treatment of female urinary incontinence (UI). EVIDENCE ACQUISITION: We conducted a comprehensive search in four internationally recognized databases (PubMed, Embase, Web of Science, Cochrane Library) for SRs/MAs pertaining to the treatment of female UI using acupuncture and its related therapies. We evaluated the methodological quality of the SRs/MAs using the "Assessing the Methodological Quality of Systematic Reviews 2" (AMSTAR-2) tool, assessed the quality of evidence using the "Grading of Recommendations, Assessment, Development, and Evaluation" (GRADE) system, and evaluated the reporting quality of the SRs/MAs using the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020" (PRISMA-2020) guidelines. This overview is registered with PROSPERO, CRD42024557600. EVIDENCE SYNTHESIS: In the final selection of 7 SRs/MAs, a consistent finding of the superiority of acupuncture and related therapies in the treatment of female UI was observed. Methodological quality was classified according to AMSTAR-2, with three rated as "high," two as "moderate," and two as "low." The main sources of downgrading included the absence of funding sources, failure to provide a reasonable explanation for heterogeneity, and not reporting potential conflicts of interest. According to the GRADE system, the quality of evidence ranged from moderate to very low. The most common reason for downgrading the evidence quality was the repeated utilization of the same original randomized controlled trials. Some results were also downgraded due to inconsistency, imprecision, and potential publication bias. According to the PRISMA-2020 statement, most SR/MAs clearly presented their title information, and almost all of them correctly used meta-analysis methods. However, some of them lacked comprehensive analysis and discussion of bias risk and consistency of results and were deficient in terms of protocol registration and documentation. CONCLUSIONS: Acupuncture and related therapies demonstrate superiority in terms of efficacy and safety for the treatment of female urinary incontinence (UI). The overall quality of the SRs/MAs seems to be satisfactory, particularly when compared to studies of acupuncture for the treatment of other conditions. However, attention should still be given to the proper use of methods and ensuring completeness in reporting.

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High seed lint fibre density is proposed as one of the breeding objectives for boosting cotton fibre yield. We identify the sources of potential lint fibre cells and discuss the opportunities and challenges involved in realizing the goal.

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Background: Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated. Methods: IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. In vitro and in vivo evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets. Results: EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers. Conclusions: Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages.

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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neovascularización Patológica , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Microambiente Tumoral/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/metabolismo , Animales , Neovascularización Patológica/metabolismo , Neovascularización Patológica/virología , Ratones , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Línea Celular Tumoral , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Quimiocina CCL5/metabolismo , Inhibidores de la Angiogénesis/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Femenino

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Glandular trichomes (GTs) play a crucial role in plant defenses and the synthesis of secondary metabolites. Understanding the developmental trajectory of GTs is essential for unraveling their functional significance and potential applications. Here we established a comprehensive single-cell atlas of Nicotiana tabacum leaves, a model plant for GT studies. The atlas included a total of 40,433 cells and successfully captured both long GTs (LGTs) and short GTs (SGTs) from Nicotiana leaves. The developmental trajectories of these trichomes were delineated, revealing potential disparities in epidermal development. Comparative analysis of Arabidopsis and Nicotiana trichome development indicated limited similarity between Arabidopsis epidermal non-glandular trichomes and Nicotiana LGTs and SGTs, implying the essentiality of studying the genes directly involved in the development of Nicotiana GTs for a proper and comprehensive understanding of GT biology. Overall, our results provide profound insights into the developmental intricacies of the specialized GTs.

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In acupuncture diagnosis and treatment, non-quantitative clinical descriptions have limited the development of standardized treatment methods. This study explores the effectiveness and the reasons for discrepancies in the entity recognition and classification of meridians in acupuncture indication using the Acupuncture Bidirectional Encoder Representations from Transformers (ACUBERT) model. During the research process, we selected 54 593 different entities from 82 acupuncture medical books as the pretraining corpus for medical literature, conducting classification research on Chinese medical literature using the BERT model. Additionally, we employed the support vector machine and Random Forest models as comparative benchmarks and optimized them through parameter tuning, ultimately leading to the development of the ACUBERT model. The results show that the ACUBERT model outperforms other baseline models in classification effectiveness, achieving the best performance at Epoch = 5. The model's "precision," "recall," and F1 scores reached above 0.8. Moreover, our study has a unique feature: it trains the meridian differentiation model based on the eight principles of differentiation and zang-fu differentiation as foundational labels. It establishes an acupuncture-indication knowledge base (ACU-IKD) and ACUBERT model with traditional Chinese medicine characteristics. In summary, the ACUBERT model significantly enhances the classification effectiveness of meridian attribution in the acupuncture indication database and also demonstrates the classification advantages of deep learning methods based on BERT in multi-category, large-scale training sets. Database URL: http://acuai.njucm.edu.cn:8081/#/user/login?tenantUrl=default.

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Terapia por Acupuntura , Meridianos , Humanos , Bases del Conocimiento , Acupuntura , Máquina de Vectores de Soporte

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Potassium ion signaling mediates microbial communication in electroactive biofilms within microbial fuel cells (MFCs), but its role in nitrogen removal remains unclear. This study investigated the impact of inhibiting potassium signaling on nitrogen removal in MFCs using tetraethylammonium chloride (TEA) as an inhibitor. Results demonstrated that 5 mM and 10 mM TEA reduced the maximum power generation of MFCs from 77.95 mW/cm2 to 57.18 mW/cm2 and 48.23 mW/cm2, respectively. Correspondingly, total nitrogen (TN) removal efficiency was decreased from 46.57 ± 1.01% to 35.93 ± 0.63% and 38.97 ± 0.74%, respectively. This decline was attributed to inhibited potassium ion signaling, which compromised the electrochemical performance of the MFC and hindered the nitrogen removal process. The relative abundance of exoelectrogen Geobactor decreased from 15.37% to 5.17% and 8.05%, while the relative abundance of cathodic nitrifying bacteria Nitrosomonas decreased from 17.87% to 4.92% and 3.63% under 5 mM and 10 mM TEA. These findings underscore the crucial role of potassium ion signaling in enhancing the bioelectrochemical nitrogen removal process in MFCs.

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Male sterility is used in the production of hybrid seeds and can improve the breeding efficiency of cotton hybrids. Reactive oxygen species is closely associated with the tapetum and pollen development, but their relationship in cotton male fertility remains unclear. In this study, we comprehensively compared the cytology and proteome of the anthers from an Upland cotton (Gossypium hirsutum) material, Shida 98 (WT), and its nearly-isogenic male sterile line Shida 98A (MS). Cytology indicated delayed PCD in the tapetum and defects in microspores in MS anthers. And further studies revealed disruption of ROS homeostasis. Proteomic analysis identified proteins with differential abundance mainly being related to redox homeostasis, protein folding, and apoptotic signaling pathways. GhAPX1 interacted with GhHSP70 and played a crucial role in the development of cotton anthers. Exogenous application of HSP70 inhibitor increased H2O2 content and decreased the activity of APX1 and pollen viability. The GhAPX1 mutants generated by CRISPR/Cas9-mediated gene editing exhibited premature degradation of the tapetum, significant decrease in pollen viability, and significant increase in H2O2 content. Altogether, our results imply HSP70 and APX1 being the key players jointly regulating male fertility by mediating ROS homeostasis. These results provide insights into the proteins associated with male fertility.

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Gossypium , Proteínas HSP70 de Choque Térmico , Homeostasis , Proteínas de Plantas , Polen , Especies Reactivas de Oxígeno , Gossypium/genética , Gossypium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Polen/genética , Polen/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/genética , Infertilidad Vegetal/genética , Fertilidad , Regulación de la Expresión Génica de las Plantas , Proteómica/métodos , Peróxido de Hidrógeno/metabolismo

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Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.

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Fenotipo , Animales , Ratones , Convulsiones/genética , Convulsiones/metabolismo , Modelos Animales de Enfermedad , Neuronas/metabolismo , Mutación Missense , Hipocampo/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos

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Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance.

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Proteína BRCA1 , Reparación del ADN , Chaperonas de Histonas , N-Metiltransferasa de Histona-Lisina , Animales , Humanos , Ratones , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Línea Celular Tumoral , Cromatina/metabolismo , Roturas del ADN de Doble Cadena , Metilación de ADN , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Chaperonas de Histonas/metabolismo , Chaperonas de Histonas/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Metilación , Metiltransferasas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Tolerancia a Radiación/genética

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INTRODUCTION: Post-stroke depression (PSD) is an emotional disease characterized by loss of interest and depression after a stroke. Acupuncture, one of the most critical non-drug therapies for the treatment of PSD, has significant clinical efficacy, but the mechanism is not fully understood. Previous study has shown that acupuncture can reduce the level of proinflammatory cytokines and increase the level of anti-inflammatory cytokines, suggesting that regulating the dynamic balance of inflammatory cytokines may be the basis for acupuncture to improve PSD symptoms. METHODS AND ANALYSIS: A total of 84 patients with PSD will be recruited and randomly assigned to one of two groups at a 1:1 ratio. Based on the conventional stroke treatment, the control group will receive XingnaoKaiqiao (XNKQ) acupuncture, and the experimental group will receive antidepressant acupuncture at the same time as XNKQ acupuncture. The intervention will last four weeks, and data will be collected before and after treatment. The Hamilton depression scale (HAMD-17) is the primary outcome measure, and the secondary outcome measures include the Self-rating Depression Scale (SDS), the National Institute of Health stroke scale (NIHSS), and the Modified Barthel Index (MBI). Serum IL-1ß, IL-4, 5-HT, and BDNF will be used as laboratory indicators. The scales will be assessed at baseline, two weeks, and four weeks, and serum items will be measured at baseline and four weeks after treatment. This study will observe the clinical effect of acupuncture on PSD and the changes in serum-related inflammatory cytokines and explore the possible mechanism of acupuncture against depression from the perspective of inflammatory response. ETHICS AND DISSEMINATION: This study protocol was approved by the Medical Ethics Committee of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (item number: TYLL2023[Z]004). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.

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Terapia por Acupuntura , Depresión , Accidente Cerebrovascular , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia por Acupuntura/métodos , Citocinas/sangre , Citocinas/metabolismo , Depresión/terapia , Depresión/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/psicología , Resultado del Tratamiento

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PURPOSE: This study aimed to explore the differential effects of varying doses of atorvastatin on antagonizing lipopolysaccharide (LPS)-induced endothelial inflammation based on heme oxygenase 1 (HO-1) expression. METHOD: Vascular endothelial inflammatory injury was induced in 40 Sprague-Dawley rats by intraperitoneal injection of LPS. These rats were randomly divided into control, low-dose atorvastatin, high-dose atorvastatin, and HO-1 blocking groups. Seven days after treatment, all rats were sacrificed, and heart-derived peripheral blood was collected to measure the serum concentrations of bilirubin, alanine aminotransferase (ALT), total cholesterol, malondialdehyde, endothelial cell protein C receptor, endothelin-1, von Willebrand factor, and soluble thrombomodulin. Meanwhile, the number of circulating endothelial cells was determined using flow cytometry. Vascular tissues from descending aorta of rats from each group were extracted to detect the expression level of HO-1. RESULTS: After different doses of atorvastatin intervention, the above inflammatory indices were decreased, and HO-1 expression and ALT concentration were increased in the atorvastatin-treated group of rats compared with the control group. These changes were more pronounced in the high-dose statin group (P < 0.05). Conversely, no significant decrease in the above inflammatory indices and no significant increase in HO-1 expression were observed in rats in the blocking group (P > 0.05). CONCLUSION: For LPS-induced vascular inflammation, high-dose atorvastatin exerts potent anti-inflammatory and vascular endothelial protection effects by inducing HO-1 expression.

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Atorvastatina , Endotelio Vascular , Lipopolisacáridos , Ratas Sprague-Dawley , Animales , Atorvastatina/farmacología , Ratas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Masculino , Hemo-Oxigenasa 1/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Alanina Transaminasa/sangre , Hemo Oxigenasa (Desciclizante)

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Epstein-Barr virus (EBV) is a ubiquitous and oncogenic virus that is associated with various malignancies and non-malignant diseases and EBV DNA detection is widely used for the diagnosis and prognosis prediction for these diseases. The dried blood spots (DBS) sampling method holds great potential as an alternative to venous blood samples in geographically remote areas, for individuals with disabilities, or for newborn blood collection. Therefore, the objective of this study was to assess the viability of detecting EBV DNA load from DBS. Matched whole blood and DBS samples were collected for EBV DNA extraction and quantification detection. EBV DNA detection in DBS presented a specificity of 100 %. At different EBV DNA viral load in whole blood, the sensitivity of EBV DNA detection in DBS was 38.78 % (≥1 copies/mL), 43.18 % (≥500 copies/mL), 58.63 % (≥1000 copies/mL), 71.43 % (≥2000 copies/mL), 82.35 % (≥4000 copies/mL), and 92.86 % (≥5000 copies/mL), respectively. These results indicated that the sensitivity of EBV DNA detection in DBS increased with elevating viral load. Moreover, there was good correlation between EBV DNA levels measured in whole blood and DBS, and on average, the viral load measured in whole blood was about 6-fold higher than in DBS. Our research firstly demonstrated the feasibility of using DBS for qualitative and semi-quantitative detection of EBV DNA for diagnosis and surveillance of EBV-related diseases.

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ADN Viral , Pruebas con Sangre Seca , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Sensibilidad y Especificidad , Carga Viral , Humanos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Carga Viral/métodos , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/sangre , ADN Viral/sangre , Pruebas con Sangre Seca/métodos , Manejo de Especímenes/métodos , Sangre/virología

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Understanding and optimizing the process of grain filling helps the quest to maximize rice (Oryza sativa L.) seed yield and quality, yet the intricate mechanisms at play remain fragmented. Transcription factors (TFs) are major players in the gene networks underlying the grain filling process. Here, we employed grain incomplete filling (OsGIF1)/cell wall invertase 2, a key gene involved in grain filling, to explore its upstream TFs and identified a bZIP family TF, OsbZIP10, to be a transcriptional activator of OsGIF1. Rice grains of the knockouts of OsbZIP10 showed increased white-core rates but lower amylose content (AC), leading to better eating and cooking qualities in all genetic backgrounds investigated, though the impact of mutations in OsbZIP10 on grain weight depended on genetic background. Multi-omics analyses suggested that, in addition to OsGIF1, multiple genes involved in different biological processes contributing to grain filling were targeted by OsbZIP10, including OsAGPS1, a gene encoding the ADP-Glc pyrophosphorylase (AGPase) small subunit, and genes contributing to homeostasis of reactive oxygen species. Distinct genetic make-up was observed in OsbZIP10 between japonica and indica rice varieties, with the majority varieties of each subspecies belonging to two different haplotypes that were closely associated with AC. Overexpressing the haplotype linked to high-AC in the low-AC genetic background increased AC. Overall, this study sheds crucial light on the significance of the OsbZIP10-OsGIF1 module in the determination of rice grain quality, offering a potential avenue for genetic engineering of rice to produce seeds with tailored attributes.

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Grano Comestible , Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , Factores de Transcripción , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Semillas/genética , Semillas/metabolismo , Amilosa/metabolismo

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Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

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Hemorragia Cerebral , Ferroptosis , Factor 2 Relacionado con NF-E2 , Nanopartículas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Selenio , Animales , Humanos , Masculino , Ratones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Modelos Animales de Enfermedad , Ferroptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/administración & dosificación , Factor 2 Relacionado con NF-E2/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Selenio/química , Selenio/farmacología , Albúmina Sérica Bovina/química

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The NAD+-dependent deacetylase SIRT7 is a pivotal regulator of DNA damage response (DDR) and a promising drug target for developing cancer therapeutics. However, limited progress has been made in SIRT7 modulator discovery. Here, we applied peptide-based deacetylase platforms for SIRT7 enzymatic evaluation and successfully identified a potent SIRT7 inhibitor YZL-51N. We initially isolated bioactive YZL-51N from cockroach (Periplaneta americana) extracts and then developed the de novo synthesis of this compound. Further investigation revealed that YZL-51N impaired SIRT7 enzymatic activities through occupation of the NAD+ binding pocket. YZL-51N attenuated DNA damage repair induced by ionizing radiation (IR) in colorectal cancer cells and exhibited a synergistic anticancer effect when used in combination with etoposide. Overall, our study not only identified YZL-51N as a selective SIRT7 inhibitor from insect resources, but also confirmed its potential use in combined chemo-radiotherapy by interfering in the DNA damage repair process.

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Introduction: There is a decline in the quality and nutritive value of eggs in aged laying hens. Fruit pomaces with high nutritional and functional values have gained interest in poultry production to improve the performance. Methods: The performance, egg nutritive value, lipid metabolism, ovarian health, and cecal microbiota abundance were evaluated in aged laying hens (320 laying hens, 345-day-old) fed on a basal diet (control), and a basal diet inclusion of 0.25%, 0.5%, or 1.0% fermented Aronia melanocarpa pomace (FAMP) for eight weeks. Results: The results show that 0.5% FAMP reduced the saturated fatty acids (such as C16:0) and improved the healthy lipid indices in egg yolks by decreasing the atherogenicity index, thrombogenic index, and hypocholesterolemia/hypercholesterolemia ratio and increasing health promotion index and desirable fatty acids (P < 0.05). Additionally, FAMP supplementation (0.25%-1.0%) increased (P < 0.05) the ovarian follicle-stimulating hormone, luteinizing hormone, and estrogen 2 levels, while 1.0% FAMP upregulated the HSD3B1 expression. The expression of VTG II and ApoVLDL II in the 0.25% and 0.5% FAMP groups, APOB in the 0.5% FAMP group, and ESR2 in the 1% FAMP group were upregulated (P < 0.05) in the liver. The ovarian total antioxidant capacity was increased (P < 0.05) by supplementation with 0.25%-1.0% FAMP. Dietary 0.5% and 1.0% FAMP downregulated (P < 0.05) the Keap1 expression, while 1.0% FAMP upregulated (P < 0.05) the Nrf2 expression in the ovary. Furthermore, 1.0% FAMP increased cecal acetate, butyrate, and valerate concentrations and Firmicutes while decreasing Proteobacteria (P < 0.05). Conclusion: Overall, FAMP improved the nutritive value of eggs in aged laying hens by improving the liver-blood-ovary function and cecal microbial and metabolite composition, which might help to enhance economic benefits.

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OBJECTIVES: To observe the effect of electroacupuncture (EA) pre-conditioning on the expression rhythm of clock gene Bmal1 in the uterine tissue of rats with controlled ovarian hyperstimulation(COH), so as to explore its mechanisms underlying improvement of the endometrial receptivity of ovarian superovulation during implantation. METHODS: Seventy-two female SD rats with typical estrous cycles were randomly divided into normal control, model and EA pre-conditioning (pre-EA) groups, with 24 rats in each group. The COH model was established by giving the rats with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) by intraperitoneal injection. The rats of the pre-EA group received EA stimulation (1 Hz/5 Hz, a tolerable strength) of "Guanyuan"(CV4) and "Sanyinjiao"(SP6) for 15 min each time, once daily (at 21：00 every day). After successive EA intervention during the first two estrous cycles, the modeling began in the third estrus cycle and the EA intervention was continued till the end of modeling, followed by raising the rats with superovulation induction and male rats undergoing vasoligation in one cage (1∶1). The rats during the estrum in the normal control group or those of the model group at the end of modeling were raised together with the male rats undergoing vasoligation in one cage. On the 5th day (04：00 AM) after raising in one cage, the rats in the three groups were sacrificed in six batches every 4 hours, with 4 rats in each group in each batch. The H.E. staining was used for revealing alterations of the endometrial thickness, number of glands and blood vessels and tissue histology, and ELISA employed to ascertain the contents of estradiol (E2) and progesterone (Pg) in serum. The expression rhythm of core clock gene Bmal1 ［In the present study, Zeitgeber time (ZT) is an artificially set laboratory time, i.e., ZT7 (07：00) is light on and ZT19 (19：00) is light off.］ and the expression of endometrial HoxA10 and leukemia inhibitory factor (LIF) mRNAs were detected by quantitative real-time PCR. The Western blot was employed to detect the expression levels of HoxA10 and LIF proteins. RESULTS: Findings of the clock gene Bmal1 level showed that the expression peak was at ZT12 and the valley value at ZT20 in the normal control group, and that of the peak value was at ZT20 and valley value at ZT12 in the model group, while in the pre-EA group, the peak value was at ZT8, and the valley value at ZT4. The difference of Bmal1 levels among the three groups was most significant at ZT12 (12：00), therefore, the tissue samples were taken at ZT12 in this study for comparison of the levels of different indexes among the 3 groups. Compared with the control group, the endometrial thickness, number of glands and blood vessels, HoxA10 and LIF mRNAs and proteins were significantly down-regulated (P<0.01, P<0.05), and contents of serum E2 and Pg were considerably up-regulated in the model group (P<0.01, P<0.05). Relevant to the model group, the pre-EA group had an apparent increase in the endometrial thickness, number of glands and blood vessels, and expression levels of HoxA10 and LIF mRNAs and proteins (P<0.05, P<0.01), and a marked decrease in the serum Pg (P<0.05). At the ZT12 (12：00 noon), compared with the normal control group, the mRNA level of Bmal1 was significantly decreased in the model group (P<0.01)；and compared with the model group, the level of Bmal1 mRNA was significantly increased in the pre-EA group (P<0.05). In addition, at the node of ZT16, the mRNA level of Bmal1 was significantly decreased in the model group in comparison with the normal control group (P<0.01). CONCLUSIONS: EA preconditioning can improve the endometrial receptivity during the implantation window period in rats with COH, which may be related to its functions in regulating the expression of clock gene Bmal1 in the uterine tissue and in correcting the disturbance of clock gene rhythm.

Asunto(s)

Factores de Transcripción ARNTL , Electroacupuntura , Ratas Sprague-Dawley , Útero , Animales , Femenino , Ratas , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Útero/metabolismo , Humanos , Masculino , Puntos de Acupuntura , Inducción de la Ovulación

RESUMEN

Conformal 3D printing can construct specific three-dimensional structures on the free-form surfaces of target objects, achieving in situ additive manufacturing and repair, making it one of the cutting-edge technologies in the current field of 3D printing. To further improve the repair efficacy in tissue engineering, this study proposes a conformal path planning algorithm for in situ printing in specific areas of the target object. By designing the conformal 3D printing algorithm and utilizing vector projection and other methods, coordinate transformation of the printing trajectory was achieved. The algorithm was validated, showing good adherence of the printing material to the target surface. In situ repair experiments were also conducted on human hands and pig tibia defect models, verifying the feasibility of this method and laying a foundation for further research in personalized medicine and tissue repair.

RESUMEN

Electrogenic biofilms, which have attracted considerable attention in simultaneous wastewater treatment and energy recovery in bioelectrochemical systems, are regulated by chemical communication and potassium channel-mediated electrical signaling. However, how these two communication pathways interact with each other has not been thoroughly investigated. This study first explored the roles of chemical communication, including intracellular bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) and extracellular N-acyl-homoserine lactone (AHL)-mediated quorum sensing, in electrogenic biofilm formation through an integrated analysis of transcriptomics and metabolomics. Electrical signaling disruption inhibited the formation and electroactivity of Geobacter sulfurreducens biofilm, which was mainly ascribed to the reduction in biofilm viability and extracellular protein/polysaccharide ratio. The upregulation of expression levels of genes encoding c-di-GMP and AHL synthesis by transcriptomic analysis, and the increased secretion of N-butanoyl-L-homoserine lactone by metabolomic analysis confirmed the enhancement of chemical communication under electrical signaling disruption, thus indicating a compensatory mechanism among different signaling pathways. Furthermore, protein-protein interaction network showed the convergence of different signaling pathways, with c-di-GMP-related genes acting as central bridges. This study highlights the interaction of different signaling pathways, especially the resilience of c-di-GMP signaling to adverse external stresses, thereby laying the foundation for facilitating electrogenic biofilm formation under adverse conditions in practical applications.