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Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.
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Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologiaRESUMO
Phosphatidylinositol 3-kinase (PI3K)-AKT and androgen receptor (AR) pathways are commonly activated in prostate cancers. Their reciprocal regulation makes advanced prostate cancers difficult to treat. The current study shows that pleckstrin-2 (PLEK-2, a proto-oncoprotein involved in the activation and stabilization of AKT, connects these two pathways. Genetic evidence is provided that suggests that Plek2 deficiency largely reverted tumorigenesis in Pten prostate-specific knockout mice and that overexpression of PLEK2 promoted the proliferation and colony formation of prostate cancer cells in vitro. In addition, it was found that PLEK2 was negatively regulated by AR, that AR transcriptionally repressed PLEK2 through binding to the PLEK2 promoter region, and that overexpression of AR reduced PLEK2 expression, which inactivated AKT. Conversely, knockdown of AR in prostate cancer cells increased PLEK2 expression and activated the AKT pathway. This reciprocal inhibitory loop can be pharmacologically targeted using the PLEK2 inhibitor. It is shown that the PLEK2 inhibitor dose-dependently inhibited prostate cancer cell proliferation with the inactivation of AKT. Overall, the current study uncovers the crucial role of PLEK2 in prostate cancer proliferation and provides the rationale for targeting PLEK2 to treat prostate cancers.
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The WRINKLED1 (WRI1) and LAFL [LEAFY COTYLEDON1 (LEC1), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2] transcription factors play essential roles in governing seed development and oil biosynthesis. To gain a comprehensive understanding of the transcriptional regulation of WRI1 and LAFL, we conducted genome-wide association studies for the expression profiles of WRI1 and LAFL in developing seeds at 20 and 40 days after flowering (DAF) using 302 rapeseed (Brassica napus) accessions. We identified a total of 237 expression quantitative trait nucleotides (eQTNs) and 51 expression QTN-by-environment interactions (eQEIs) associated with WRI1 and LAFL. Around these eQTNs and eQEIs, we pinpointed 41 and 8 candidate genes with known transcriptional regulations or protein interactions with their expression traits, respectively. Based on RNA-seq and ATAC-seq data, we employed the XGBoost and Basenji models which predicted 15 candidate genes potentially regulating the expression of WRI1 and LAFL. We further validated the predictions via tissue expression profile, haplotype analysis, and expression correlation analysis, and verified the transcriptional activation activity of BnaC03.MYB56 (R2R3-MYB transcription factor 56) on the expression of BnaA09.LEC1 by dual-luciferase reporter and yeast one-hybrid assays. BnaA10.AGL15 (AGAMOUS-LIKE 15), BnaC04.VAL1 (VIVIPAROUS1/ABSCISIC ACID INSENSITIVE3-LIKE 1), BnaC03.MYB56, and BnaA10.MYB56 were co-expressed with WRI1 and LAFL at 20 DAF in M35, a key module for seed development and oil biosynthesis. We further validated the positive regulation of MYB56 on seed oil accumulation using Arabidopsis (Arabidopsis thaliana) mutants. This study not only delivers a framework for future eQEI identification but also offers insights into the developmental regulation of seed oil accumulation.
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While lead sulfide shows notable thermoelectric properties, its production costs remain high, and its mechanical hardness is low, which constrains its commercial viability. Herein, we demonstrate a straightforward and cost-effective method to produce PbS nanocrystals at ambient temperature. By introducing controlled amounts of silver, we achieve p-type conductivity and fine-tune the energy band structure and lattice configuration. Computational results show that silver shifts the Fermi level into the valence band, facilitating band convergence and thereby enhancing the power factor. Besides, excess silver is present as silver sulfide, which effectively diminishes the interface barrier and enhances the Seebeck coefficient. Defects caused by doping, along with dislocations and interfaces, reduce thermal conductivity to 0.49 W m-1 K-1 at 690 K. Moreover, the alterations in crystal structure and chemical composition enhance the PbS mechanical properties. Overall, optimized materials show thermoelectric figures of merit approximately 10-fold higher than that of pristine PbS, alongside an average hardness of 1.08 GPa.
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A kagome lattice hosts a plethora of quantum states arising from the interplay between nontrivial topology and electron correlations. The recently discovered kagome magnet RMn6Sn6 (R represents a rare-earth element) is believed to showcase a kagome band closely resembling textbook characteristics. Here, we report the characterization of local electronic states and their magnetization response in YMn6Sn6 via scanning tunneling microscopy measurements under vector magnetic fields. Our spectroscopic maps reveal a spontaneously trimerized kagome electronic order in YMn6Sn6, where the 6-fold rotational symmetry is disrupted while translational symmetry is maintained. Further application of an external magnetic field demonstrates a strong coupling of the YMn6Sn6 kagome band to the field, which exhibits an energy shift discrepancy under different field directions, implying the existence of magnetization-response anisotropy and anomalous g factors. Our findings establish YMn6Sn6 as an ideal platform for investigating kagome-derived orbital magnetic moment and correlated magnetic topological states.
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In the heterostructure of two-dimensional (2D) materials, many novel physics phenomena are strongly dependent on the Moiré superlattice. How to achieve the continuous manipulation of the Moiré superlattice in the same sample is very important to study the evolution of various physical properties. Here, in minimally twisted monolayer-multilayer graphene, we found that bubble-induced strain has a huge impact on the Moiré superlattice. By employing the AFM tip to dynamically and continuously move the nanobubble, we realized the modulation of the Moiré superlattice, like the evolution of regular triangular domains into long strip domain structures with single or double domain walls. We also achieved controllable modulation of the Moiré superlattice by moving multiple nanobubbles and establishing the coupling of nanobubbles. Our work presents a flexible method for continuous and controllable manipulation of Moiré superlattices, which will be widely used to study novel physical properties in 2D heterostructures.
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The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.
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BACKGROUND: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels. METHODS: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019. RESULTS: The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income. CONCLUSIONS: Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.
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Carga Global da Doença , Acidente Vascular Cerebral , Humanos , Adolescente , Criança , Pré-Escolar , Feminino , Masculino , Lactente , Acidente Vascular Cerebral/epidemiologia , Carga Global da Doença/tendências , Adulto Jovem , Incidência , Recém-Nascido , Saúde Global , Fatores de Risco , Prevalência , Acidente Vascular Cerebral Hemorrágico/epidemiologia , AVC Isquêmico/epidemiologia , Hemorragia Cerebral/epidemiologia , Efeitos Psicossociais da DoençaRESUMO
Group 2 innate lymphoid cells (ILC2s) play a crucial role in the progression of asthma, yet the regulatory mechanisms modulating ILC2 responses in asthma remain underexplored. Human milk oligosaccharides (HMOs), vital non-nutritive components of breast milk, are known to significantly shape immune system development and influence the incidence of allergic diseases. However, their impact on ILC2-driven asthma is not fully understood. Our research reveals that dietary HMOs act as potent inhibitors of ILC2 responses and allergic airway inflammation. Treatment with 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) significantly reduced ILC2-related airway inflammation induced by papain or Alternaria alternata in mice, evidenced by decreased eosinophil (EOS) infiltration and lower IL-5 and IL-13 levels in BALF. Notably, while ILC2 expresses HMO receptors, HMO did not act directly on ILC2 but potentially modulated their activity through alterations in gut microbiota derived SCFAs. HMO treatments alleviated airway inflammation in SCFA-dependent manners, with SCFA depletion or receptor blocking reversing these beneficial effects. This study reveals the potential of dietary HMOs in managing asthma through modulation of ILC2 activity and the gut-lung axis, proposing a new therapeutic avenue that utilises the immunomodulatory capacities of nutritional components to combat respiratory diseases.
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Fusarium head blight (FHB) stands out as one of the most devastating wheat diseases and leads to significantly grain yield losses and quality reductions in epidemic years. Exploring quantitative trait loci (QTL) for FHB resistance is a critical step for developing new FHB-resistant varieties. We previously constructed a genetic map of unigenes (UG-Map) according to the physical positions using a set of recombinant-inbred lines (RILs) derived from the cross of 'TN18 × LM6' (TL-RILs). Here, the number of diseased spikelets (NDS) and relative disease index (RDI) for FHB resistance were investigated under four environments using TL-RILs, which were distributed across 13 chromosomes. A number of 36 candidate genes for NDS and RDI from of 19 stable QTLs were identified. The average number of candidate genes per QTL was 1.89, with 14 (73.7%), two (10.5%), and three (15.8%) QTLs including one, two, and 3-10 candidate genes, respectively. Among the 24 candidate genes annotated in the reference genome RefSeq v1.1, the homologous genes of seven candidate genes, including TraesCS4B02G227300 for QNds/Rdi-4BL-4553, TraesCS5B02G303200, TraesCS5B02G303300, TraesCS5B02G303700, TraesCS5B02G303800 and TraesCS5B02G304000 for QNds/Rdi-5BL-9509, and TraesCS7A02G568400 for QNds/Rdi-7AL-14499, were previously reported to be related to FHB resistance in wheat, barely or Brachypodium distachyon. These genes should be closely associated with FHB resistance in wheat. In addition, the homologous genes of five genes, including TraesCS1A02G037600LC for QNds-1AS-2225, TraesCS1D02G017800 and TraesCS1D02G017900 for QNds-1DS-527, TraesCS1D02G018000 for QRdi-1DS-575, and TraesCS4B02G227400 for QNds/Rdi-4BL-4553, were involved in plant defense responses against pathogens. These genes should be likely associated with FHB resistance in wheat.
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Mapeamento Cromossômico , Resistência à Doença , Fusarium , Doenças das Plantas , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/microbiologia , Locos de Características Quantitativas/genética , Fusarium/fisiologia , Fusarium/patogenicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Resistência à Doença/genética , Genes de Plantas , Cromossomos de Plantas/genéticaRESUMO
Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.
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Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Proteína Potenciadora do Homólogo 2 de Zeste , Epigênese Genética , Ferroptose , Neoplasias Hepáticas , Sorafenibe , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Resistencia a Medicamentos Antineoplásicos/genética , Células Hep G2 , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Animais , Piridonas/farmacologia , Piridonas/uso terapêutico , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Morfolinas/farmacologia , Benzamidas , Compostos de BifeniloRESUMO
BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Metilação de DNA , Detecção Precoce de Câncer , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Triagem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
Aqueous ammonium ion batteries (AAIBs) have garnered significant attention due to their unique energy storage mechanism. However, their progress is hindered by the relatively low capacities of NH4 + host materials. Herein, the study proposes an electrodeposited tungsten oxide@polyaniline (WOx@PANI) composite electrode as a NH4 + host, which achieves an ultrahigh capacity of 280.3 mAh g-1 at 1 A g-1, surpassing the vast majority of previously reported NH4 + host materials. The synergistic interaction of coordination chemistry and hydrogen bond chemistry between the WOx and PANI enhances the charge storage capacity. Experimental results indicate that the strong interfacial coordination bonding (N: âW6+) effectively modulates the chemical environment of W atoms, enhances the protonation level of PANI, and thus consequently the conductivity and stability of the composites. Spectroscopy analysis further reveals a unique NH4 +/H+ co-insertion mechanism, in which the interfacial hydrogen bond network (N-H···O) accelerates proton involvement in the energy storage process and activates the Grotthuss hopping conduction of H+ between the hydrated tungsten oxide layers. This work opens a new avenue to achieving high-capacity NH4 + storage through interfacial chemistry interactions, overcoming the capacity limitations of NH4 + host materials for aqueous energy storage.
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Manganese dioxide (MnO2) materials have recently garnered attention as prospective high-capacity cathodes, owing to their theoretical two-electron redox reaction in charge storage processes. However, their practical application in aqueous energy storage systems faces a formidable challenge: the disproportionation of Mn3+ ions, leading to a significant reduction in their capacity. To address this limitation, the study presents a novel graphitic carbon interlayer-engineered manganese oxide (CI-MnOx) characterized by an open structure and abundant defects. This innovative material serves several essential functions for efficient aqueous energy storage. First, a graphitic carbon layer coats the MnOx molecular interlayer, effectively inhibiting Mn3+ disproportionation and substantially enhancing electrode conductivity. Second, the phase variation within MnOx generates numerous crystal defects, vacancies, and active sites, optimizing electron-transfer capability. Third, the flexible carbon layer acts as a buffer, mitigating the volume expansion of MnOx during extended cycling. The synergistic effects of these features result in the CI-MnOx exhibiting an impressive high capacity of 272 mAh g-1 (1224 F g-1) at 0.25 A g-1. Notably, the CI-MnOx demonstrates zero capacity loss after 90 000 cycles (≈3011 h), an uncommon longevity for manganese oxide materials. Spectral characterizations reveal reversible cation intercalation and conversion reactions with multielectron transfer in a LiCl electrolyte.
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Developing novel proton exchange membranes (PEMs) with low cost and superior performance to replace Nafion is of great significance. Polyoxometalate-doped sulfonated poly(aryl ether ketone sulfone) (SPAEKS) allows for the amalgamation of the advantages in each constituent, thereby achieving an optimized performance for the hybrid PEMs. Herein, the hybrid membranes by introducing 2MeIm-{Mo132} into SPAEKS are obtained. Excellent hydrophilic properties of 2MeIm-{Mo132} can help more water molecules be retained in the hybrid membrane, providing abundant carriers for proton transport and proton hopping sites to build successive hydrophilic channels, thus lowering the energy barrier, accelerating the proton migration, and significantly fostering the proton conductivity of hybrid membranes. Especially, SP-2MIMo132-5 exhibits an enhanced proton conductivity of 75 mS cm-1 at 80 °C, which is 82.9% higher than pristine SPAEKS membrane. Additionally, this membrane is suitable for application in proton exchange membrane fuel cells, and a maximum power density of 266.2 mW cm-2 can be achieved at 80 °C, which far exceeds that of pristine SPAEKS membrane (54.6 mW cm-2). This work demonstrates that polyoxometalate-based clusters can serve as excellent proton conduction sites, opening up the choice of proton conduction carriers in hybrid membrane design and providing a novel idea to manufacture high-performance PEMs.
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INTRODUCTION: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. METHODS: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. RESULTS: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. CONCLUSIONS: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/genética , Colangiocarcinoma/cirurgia , Prognóstico , Perfilação da Expressão Gênica , Hepatectomia , Genômica , Ductos Biliares Intra-Hepáticos/patologia , Antígenos de Histocompatibilidade Menor , Histona DesmetilasesRESUMO
An ultra-broadband TM-pass polarizer is designed, fabricated, and experimentally demonstrated based on subwavelength grating (SWG) metamaterials in a lithium niobate on an insulator (LNOI) platform. According to our simulation, the designed device is predicted to work at a 220â nm wavelength range from 1460 to 1680â nm, covering the S-, C-, L-, U-bands of optical fiber communication. By depositing and subsequently etching a silicon nitride thin film atop the LNOI chip, the SWG structures are formed successfully by using complementary metal-oxide semiconductor (CMOS)-compatible fabrication processes. The measured results show a high polarization extinction ratio larger than 20â dB and a relatively low insertion loss below 2.5â dB over a 130â nm wavelength range from 1500 to 1630â nm, mainly limited by the operation bandwidth of our laser source.
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Photonic integrated circuits have garnered significant attention and experienced rapid development in recent years. To provide fundamental building blocks for scalable optical classical and quantum information processing, one important direction is to develop cryogenic compatible photonic integrated devices. Here, we prepare one optical filter on a lithium-niobate-on-insulator (LNOI) platform based on a multimode waveguide grating and verify its availability at temperature from 295 to 7 K. We find that the integrated optical filter still shows good quality under cryogenic conditions, and the shift of the working wavelength at different temperatures is well explained by the index variation of the material. These results advance LNOI integrated optical devices in applications under cryogenic conditions.
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Cavity magnonics is an emerging research area focusing on the coupling between magnons and photons. Despite its great potential for coherent information processing, it has been long restricted by the narrow interaction bandwidth. In this Letter, we theoretically propose and experimentally demonstrate a novel approach to achieve broadband photon-magnon coupling by adopting slow waves on engineered microwave waveguides. To the best of our knowledge, this is the first time that slow wave is combined with hybrid magnonics. Its unique properties promise great potentials for both fundamental research and practical applications, for instance, by deepening our understanding of the light-matter interaction in the slow wave regime and providing high-efficiency spin wave transducers. The device concept can be extended to other systems such as optomagnonics and magnomechanics, opening up new directions for hybrid magnonics.
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BACKGROUND: The hemodynamics of the cerebral sinuses play a vital role in understanding blood flow-related diseases, yet the hemodynamics of the cerebral sinuses in normal adults remains an unresolved issue. PURPOSE: To evaluate hemodynamics in the cerebral sinus of adults using 4-dimensional flow MRI (4D Flow MRI). STUDY TYPE: Cross-sectional. POPULATION: Ninety-nine healthy volunteers (mean age, 42.88 ± 13.16 years old; females/males, 55/44). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: The blood flow velocity, average blood flow rate (Q), and vortexes at the superior sagittal sinus (SSS), straight sinus (STS), transverse sinus, sigmoid sinus, and jugular bulb of each volunteer were evaluated by two independent neuroradiologists. The relationship between the total cerebral Q and sex and age was also assessed. Twelve volunteers underwent two scans within a month. STATISTICAL TESTS: The intraclass correlation coefficient (ICC) evaluated the inter-observer agreement. Blood flow parameters among volunteers were compared by the independent-sample t-test or Mann-Whitney U test. The multiple linear regression equation was used to evaluate the relationship between total cerebral Q and age and sex. P < 0.05 indicated statistical significance. RESULTS: The test-retest and interobserver reliability of average velocity and Q were moderate to high (ICC: 0.54-0.99). Cerebral sinus velocity varied by segment and cardiac cycle. The SSS's velocity and Q increased downstream and Q near torcular herophili was 3.5 times that through the STS. The total cerebral Q decreased by 0.06 mL/s per year (ß = -0.06 ± 0.013) and was sex-independent within the group. Vortexes were found in 12.12%, 8.9%, and 59.8% of torcular herophili, transverse-sigmoid junction, and jugular bulb, respectively, and were related to higher upstream flow. DATA CONCLUSION: Cerebral sinuses could be measured visually and quantitatively in vivo by 4D Flow MRI, providing a basis for future research on pulsating tinnitus, multiple sclerosis, and other related diseases. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.