178 research outputs found

    The silent spread: exploring diverse metastatic pathways in high-grade serous ovarian cancer

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    High-grade serous ovarian cancer (HGSOC) is a highly aggressive and deadly gynecological cancer, with metastasis being a key factor in its poor prognosis. Historically, HGSOC was thought to spread primarily through the peritoneal cavity, but recent research has revealed additional routes of metastasis, including the blood and lymphatic systems. This review discusses the complex processes of HGSOC metastasis, focusing on peritoneal immune suppression, stromal reprogramming, and the role of circulating tumor cells in blood-based spread. We also explore the clinical significance of lymphatic metastasis, particularly its impact on patient outcomes. Gaining insight into molecular and genetic drivers, such as BRCA mutations and interactions within the immune microenvironment, is essential for developing targeted treatments. Future studies should aim to enhance experimental models, identify early detection markers, and investigate novel therapeutic approaches to effectively address HGSOC metastasis and improve patient survival

    High-mobility graphene on liquid p-block elements by ultra-low-loss CVD growth

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    The high-quality and low-cost of the graphene preparation method decide whether graphene is put into the applications finally. Enormous efforts have been devoted to understand and optimize the CVD process of graphene over various d-block transition metals (e.g. Cu, Ni and Pt). Here we report the growth of uniform high-quality single-layer, single-crystalline graphene flakes and their continuous films over p-block elements (e.g. Ga) liquid films using ambient-pressure chemical vapor deposition. The graphene shows high crystalline quality with electron mobility reaching levels as high as 7400 cm2 V−1s−1 under ambient conditions. Our employed growth strategy is ultra-low-loss. Only trace amounts of Ga are consumed in the production and transfer of the graphene and expensive film deposition or vacuum systems are not needed. We believe that our research will open up new territory in the field of graphene growth and thus promote its practical application

    Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis

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    Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition

    Room-temperature conversion of ethane and the mechanism understanding over single iron atoms confined in graphene

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    Abstract(#br)The catalytic conversion of ethane to high value-added chemicals is significantly important for utilization of hydrocarbon resources. However, it is a great challenge due to the typically required high temperature (> 400 °C) conditions. Herein, a highly active catalytic conversion process of ethane at room temperature (25 °C) is reported on single iron atoms confined in graphene via the porphyrin-like N 4 -coordination structures. Combining with the operando time of flight mass spectrometer and density functional theory calculations, the reaction is identified as a radical mechanism, in which the C–H bonds of the same C atom are preferentially and sequentially activated, generating the value-added C 2 chemicals, simultaneously avoiding the over-oxidation of the products to CO 2 . The in-situ formed O–FeN 4 –O structure at the single iron atom serves as the active center for the reaction and facilitates the formation of ethyl radicals. This work deepens the understanding of alkane C–H activation on the FeN 4 center and provides the reference in development of efficient catalyst for selective oxidation of light alkane

    Microbial Community Succession and Response to Environmental Variables During Cow Manure and Corn Straw Composting

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    In composting system, the composition of microbial communities is determined by the constant change in the physicochemical parameters. This study explored the dynamics of bacterial and fungal communities during cow manure and corn straw composting using high throughput sequencing technology. The relationships between physicochemical parameters and microbial community composition and abundance were also evaluated. The sequencing results revealed the major phyla included Proteobacteria, Bacteroidetes, Firmicutes, Chloroflexi and Actinobacteria, Ascomycota, and Basidiomycota. Linear discriminant analysis effect size (LEfSe) illustrated that Actinomycetales and Sordariomycetes were the indicators of bacteria and fungi in the maturation phase, respectively. Mantel test showed that NO3--N, NH4+-N, TN, C/N, temperature and moisture content significantly influenced bacterial community composition while only TN and moisture content had a significant effect on fungal community structure. Structural equation model (SEM) indicated that TN, NH4+-N, NO3--N and pH had a significant effect on fungal abundance while TN and temperature significantly affected bacterial abundance. Our finding increases the understanding of microbial community succession in cow manure and corn straw composting under natural conditions

    Differential impact of biologically effective dose in distal versus proximal gamma knife targets for trigeminal neuralgia

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    We report the results of a long-term follow-up series in our center to verify the impact of biologically effective dose (BED) on the efficacy and safety of Gamma Knife radiosurgery (GKS) in the treatment of primary trigeminal neuralgia (TN). A total of 138 consecutive cases of primary TN receiving GKS were included. A 4-mm collimator was used for all cases, and a median central dose of 85 Gy (range 70–90 Gy) was prescribed. The Barrow Neurological Institute Pain Scale was adopted to evaluate the severity of TN. The median follow-up period was 65.5 months (range 12–147 months). Overall, 123 (89.1%) patients eventually achieved effective relief. The influence of BED on treatment outcomes varied by target location. For patients with distal targets, BED was a significant predictor of treatment failure (OR: 0.996, 95% CI: 0.992–0.999, p = 0.02) and post-GKS complications (OR: 1.002, 95% CI: 1.000–1.004, p = 0.01). However, BED did not significantly influence outcomes in the proximal target subgroup, either for treatment failure or complications. No significant association was found between BED and long-term outcomes in the entire cohort or in any subgroup analysis. Adjusting GKS doses according to BED for the distal target may optimize clinical outcomes in TN patients

    Dimensionality crossover to 2D vestigial nematicity from 3D zigzag antiferromagnetism in an XY-type honeycomb van der Waals magnet

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    Fluctuations and disorder effects are substantially enhanced in reduced dimensionalities. While they are mostly considered as the foe for long-range orders, fluctuations and disorders can also stimulate the emergence of novel phases of matter, for example, vestigial orders. Taking 2D magnetism as a platform, existing efforts have been focused on maintaining 2D long-range magnetic orders by suppressing fluctuations, whereas the other side, exploiting fluctuations for realizing new 2D magnetic phases, remains as an uncharted territory. Here, using a combination of NV spin relaxometry, optical spectroscopy, and Monte Carlo simulations, we report, in an XY-type honeycomb magnet NiPS3, the phase transition from the zigzag AFM order in 3D bulk to a new Z3 vestigial Potts-nematicity in 2D few layers. Spin fluctuations are shown to significantly enhance over the GHz-THz range as the layer number of NiPS3 reduces, using the NV spin relaxometry and the optical Raman quasi-elastic scattering. As a result, the Raman signatures of the zigzag AFM for bulk NiPS3, a zone-folded phonon at ~30cm-1 from the broken translational symmetry (PBTS) and a degeneracy lift of two phonons at ~180cm-1 for the broken 3-fold rotational symmetry (PBRS), evolve into the disappearance of PBTS and the survival of PBRS in few-layer NiPS3, with a critical thickness of ~10nm. The optical linear dichroism microscopy images all three nematic domain states in a single few-layer NiPS3 flake. The large-scale Monte Carlo simulations for bilayer NiPS3 model confirms the absence of long-range zigzag AFM order but the formation of the Z3 vestigial Potts-nematic phase, corroborating with the experimental finding. Our results demonstrate the positivity of strong fluctuations in creating new phases of matter after destroying more conventional ones, and offer an unprecedented pathway for developing novel 2D phases

    Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer’s disease: insights from GWAS and single-cell transcriptomics

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    BackgroundAging is an important factor in the development of Alzheimer’s disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD.MethodsThe study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes.ResultsA correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD.ConclusionWe explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation

    Heterozygous variants in PLCG1 affect hearing, vision, cardiac, and immune function

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    Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca2+ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these variants in vivo, we generated the analogous variants in the Drosophila ortholog, small wing (sl). We created a null allele slT2A and assessed its expression pattern. sl is broadly expressed, including wing discs, eye discs, and a subset of neurons and glia. slT2A mutant flies exhibit wing size reductions, ectopic wing veins, and supernumerary photoreceptors. We document that mutant flies also exhibit a reduced lifespan and age-dependent locomotor defects. Expressing wild-type sl in slT2A mutant flies rescues the loss-of-function phenotypes, whereas the variants increase lethality. Ectopic expression of an established hyperactive PLCG1 variant, p.(Asp1165His) in the wing pouch causes elevated Ca2+ activity and severe wing phenotypes. These phenotypes are also observed when the p.(Asp1019Gly) or p.(Asp1165Gly) variants are overexpressed in the wing pouch, arguing that these are gain-of-function variants. However, the wing phenotypes associated with p.(His380Arg) or p.(Leu597Phe) overexpression are either mild or only partially penetrant. Our data suggest that the heterozygous missense variants reported here affect protein function differentially and contribute to the clinical features observed in the affected individuals

    An Overview of Chassis Dynamometer in the Testing of Vehicle Emission

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    Air pollution is a risk to health and the vehicle emission is becoming a serious cause of the air pollution. Vehicle emission is influenced by many factors. The measurement of the vehicle emission can be achieved by the chassis dynamometer which can simulate the driving on the real road. The chassis-dynamometer-based testing can provide a repeatable experiment and precise emission evaluation under various driving condition. In this paper, we review the testing of vehicle emission based on a chassis dynamometer. The investigation results manifest that advance testing method for achieving the real-world driving resistance should be studied and better data analysis method should be proposed to get a more reasonable driving cycle
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