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1.
Nature ; 626(7999): 523-528, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356068

RESUMO

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

2.
Nucleic Acids Res ; 51(10): 4774-4790, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-36929421

RESUMO

Normal erythropoiesis requires the precise regulation of gene expression patterns, and transcription cofactors play a vital role in this process. Deregulation of cofactors has emerged as a key mechanism contributing to erythroid disorders. Through gene expression profiling, we found HES6 as an abundant cofactor expressed at gene level during human erythropoiesis. HES6 physically interacted with GATA1 and influenced the interaction of GATA1 with FOG1. Knockdown of HES6 impaired human erythropoiesis by decreasing GATA1 expression. Chromatin immunoprecipitation and RNA sequencing revealed a rich set of HES6- and GATA1-co-regulated genes involved in erythroid-related pathways. We also discovered a positive feedback loop composed of HES6, GATA1 and STAT1 in the regulation of erythropoiesis. Notably, erythropoietin (EPO) stimulation led to up-regulation of these loop components. Increased expression levels of loop components were observed in CD34+ cells of polycythemia vera patients. Interference by either HES6 knockdown or inhibition of STAT1 activity suppressed proliferation of erythroid cells with the JAK2V617F mutation. We further explored the impact of HES6 on polycythemia vera phenotypes in mice. The identification of the HES6-GATA1 regulatory loop and its regulation by EPO provides novel insights into human erythropoiesis regulated by EPO/EPOR and a potential therapeutic target for the management of polycythemia vera.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Eritropoese , Fator de Transcrição GATA1 , Proteínas Repressoras , Animais , Humanos , Camundongos , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Eritroides/metabolismo , Fator de Transcrição GATA1/metabolismo , Perfilação da Expressão Gênica , Policitemia Vera/genética , Policitemia Vera/metabolismo , Proteínas Repressoras/metabolismo
3.
Proc Natl Acad Sci U S A ; 119(16): e2110500119, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35412892

RESUMO

Metastasis contributes to the dismal prognosis of bladder cancer (BLCA). The mechanical status of the cell membrane is expected to mirror the ability of cell migration to promote cancer metastasis. However, the mechanical characteristics and underlying molecular profile associated with BLCA metastasis remain obscure. To study the unique cellular architecture and traits associated with cell migration, using a process called cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) we generated an aptamer-based molecular probe, termed spl3c, which identified cytoskeleton-associated protein 4 (CKAP4). CKAP4 was associated with tumor metastasis in BLCA, but we also found it to be a mechanical regulator of BLCA cells through the maintenance of a central-to-peripheral gradient of stiffness on the cell membrane. Notably, such mechanical traits were transportable through exosome-mediated intercellular CKAP4 trafficking, leading to significant enhancement of migration in recipient cells and, consequently, aggravating metastatic potential in vivo. Taken together, our study shows the robustness of this aptamer-based molecular tool for biomarker discovery, revealing the dominance of a CKAP4-induced central-to-peripheral gradient of membrane stiffness that benefits cell migration and delineating the role of exosomes in mediating mechanical signaling in BLCA metastasis.


Assuntos
Exossomos , Mecanotransdução Celular , Proteínas de Membrana , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Movimento Celular , Exossomos/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Prognóstico , Técnica de Seleção de Aptâmeros , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
4.
BMC Genomics ; 25(1): 634, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918701

RESUMO

BACKGROUND: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. RESULTS: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. CONCLUSIONS: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.


Assuntos
Adenosina , Adipogenia , Homólogo AlkB 5 da RNA Desmetilase , Galinhas , Fosfatidilcolina-Esterol O-Aciltransferase , Estabilidade de RNA , Animais , Adipogenia/genética , Galinhas/genética , Galinhas/metabolismo , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Feminino , Adenosina/análogos & derivados , Adenosina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metilação
5.
J Am Chem Soc ; 146(7): 4958-4972, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38334752

RESUMO

Temperature is a critical parameter in chemical conversion, significantly affecting the reaction kinetics and thermodynamics. Measuring temperature inside catalyst particles of industrial interest (∼micrometers to millimeters), which is crucial for understanding the evolution of chemical dynamics at catalytic active sites during reaction and advancing catalyst designs, however, remains a big challenge. Here, we propose an approach combining two-photon confocal microscopy and state-of-the-art upconversion luminescence (UL) imaging to measure the spatiotemporal-resolved temperature within individual catalyst particles in the industrially significant methanol-to-hydrocarbons reaction. Specifically, catalyst particles containing zeolites and functional nanothermometers were fabricated using microfluidic chips. Our experimental results directly demonstrate that the zeolite density and particle size can alter the temperature distribution within a single catalyst particle. Importantly, the observed temperature heterogeneity plays a decisive role in the activation of the reaction intermediate and the utilization of active sites. We expect that this work opens a venue for unveiling the reaction mechanism and kinetics within industrial catalyst particles by considering temperature heterogeneity.

6.
J Am Chem Soc ; 146(1): 319-329, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38129955

RESUMO

Tumor invasion and metastasis are the main causes of tumor progression and are the leading causes of death among cancer patients. In the present study, we propose a strategy to regulate cellular signaling with a tumor metastasis-relevant cytoskeleton-associated protein 4 (CKAP4) specific aptamer for the achievement of tumor metastasis inhibition. The designed aptamer could specifically bind to CKAP4 in the cell membranes and cytoplasm to block the internalization and recycling of α5ß1 integrin, resulting in the disruption of the fibronectin-dependent cell adhesion and the weakening of the cell traction force. Moreover, the aptamer is able to impede the interaction between CKAP4 and Dickkopf1 (DKK1) to further block the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which subsequently reduces AKT phosphorylation and inhibits the reorganization of the actin cytoskeleton in cell migration. The synergetic function of the designed aptamer in inhibiting cancer cell adhesion and blocking the PI3K signaling pathway enables efficient tumor cell metastasis suppression. The aptamer with specific targeting ability in regulating cellular signaling paves the way for cancer treatment and further provides a guiding ideology for inhibiting tumor metastasis.


Assuntos
Neoplasias , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Membrana Celular/metabolismo , Movimento Celular , Neoplasias/metabolismo
7.
Opt Express ; 32(1): 662-676, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175090

RESUMO

We propose and demonstrate a high-performance refractive Fresnel liquid crystal (LC) lens with a simple electrode design. The interconnected circular electrodes enable the creation of a parabolic voltage distribution within each Fresnel zone using only two driving voltages. By controlling these voltages within the linear response region of LC material, the desired parabolic phase profile can be achieved. We provide a detailed discussion on the electrode structure design methodology and operating principles of the lens. In our experiments, we constructed a four-zone Fresnel LC lens with a total aperture of 8 mm. The results show that the optical power of the lens can be continuously adjusted from -1.30 D to +1.33 D. Throughout the process of electrically tuning the optical power, the phase distribution within each Fresnel zone maintains a parabolic profile. These results demonstrate the high-performance of the proposed Fresnel LC lens.

8.
Opt Express ; 32(5): 7220-7242, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439409

RESUMO

A lightfield camera prototype is constructed by directly coupling a liquid-crystal (LC) microlens array with an arrayed photosensitive sensor for performing a LC-guided refocusing-rendering imaging attached by computing disparity map and extracting featured contours of targets. The proposed camera prototype presents a capability of efficiently selecting the imaging clarity value of the electronic targets interested. Two coefficients of the calibration coefficient k and the rendering coefficient C are defined for quantitively adjusting LC-guided refocusing-rendering operations about the images acquired. A parameter Dp is also introduced for exactly expressing the local disparity of the electronic patterns selected. A parallel computing architecture based on common GPU through the OpenCL platform is adopted for improving the real-time performance of the imaging algorithms proposed, which can effectively be used to extract the pixel-leveled disparity and the featured target contours. In the proposed lightfield imaging strategy, the focusing plane can be easily selected and/or further adjusted by loading and/or varying the signal voltage applied over the LC microlenses for realizing a rapid or even intelligent autofocusing. The research lays a solid foundation for continuously developing or upgrading current lightfield imaging approaches.

9.
Opt Lett ; 49(12): 3364-3367, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875621

RESUMO

High-performance atomic magnetometers (AMs) rely on the measurement of optical rotation, which requires a set of bulky polarization optics that limit their applications in scenarios where portability and compactness are necessary. In this study, a miniaturized AM is constructed based on a cubic 87Rb vapor cell and monolithic metalens, which provides an integrated scheme to achieve optical rotation detection induced by the circular birefringence of polarized atoms. The designed metalens achieves polarization splitting with deflection angles of ±10∘ and focusing with efficiencies of approximately 30% for orthogonal linear polarizations. The sensitivity of our compact device is ∼30 fT/Hz1/2 with a dynamic range of around ±1.45 nT. We envision that the presented approach paves the way for the chip integration of emerging atomic devices, which are in demand for applications such as biomagnetic imaging and portable atomic gyroscopes.

10.
Environ Res ; 253: 119153, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763283

RESUMO

Residual heavy metals in soils will destroy microbial community stability and influence its aggregation. However, exploring microbial ecology under heavy-metal stress still requires a conjoint analysis of bacterial interspecies communication and the community diversity maintenance mechanism. In this study, soil samples were collected from a heavy-metal-contaminated site in China to investigate the ecological response of indigenous microbial communities through high-throughput sequencing. Results showed that bacterial taxa and functions generated unusual decoupling phenomena. There were no significant differences in the diversity of species with the increase in concentration of heavy metals (Hg, Se, and Cr), but the functional diversity was lost. Also, the average niche breadth of bacterial species increased from 1.70 to 2.28, but community stability declined and the species assembly was always a deterministic process (NST <0.5). After the bacterial functional assembly changed from a stochastic process to a deterministic process (NST <0.5), it was transformed into a stochastic process (NST >0.5) again under the stress of high-concentration heavy metals, indicating that the collective stress resistance of bacterial communities changed from positive mutation into passive functional propagation. The research results can provide new insight into understanding the adaptive evolution of communities and ecosystem restoration under the stress of soil heavy metals.


Assuntos
Bactérias , Metais Pesados , Microbiologia do Solo , Poluentes do Solo , Metais Pesados/toxicidade , Metais Pesados/análise , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Bactérias/genética , Bactérias/classificação , Bactérias/efeitos dos fármacos , China , Processos Estocásticos , Microbiota/efeitos dos fármacos
11.
Appl Opt ; 63(2): 415-422, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227237

RESUMO

This study explores the utilization of a liquid crystal lens with a shiftable axis for true-color and super-resolution imaging. By maintaining the optical power and shifting the axis of the liquid crystal lens, precise sub-pixel level shifts are applied to the images formed on the sensor, enabling the construction of true-color and super-resolution images. A comparative analysis with the traditional interpolation-based demosaicing method reveals that true-color imaging not only enhances clarity and effective pixel count, but also significantly reduces occurrences of false color, edge aliasing, and color moiré artifacts.

12.
BMC Public Health ; 24(1): 425, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336690

RESUMO

OBJECTIVE: To translate the Stressors in Breast Cancer Scale (SBCS) from English to Chinese and assess its psychometric properties. METHODS: The Brislin's translation model was applied to perform forward translation, back translation, cross-cultural adaptation, Whereas the Chinese version of the SBCS was formed by conducting pre-testing. A cohort of 878 breast cancer patients participated in this methodological study. Content validity, construct validity, convergent validity, discriminant validity, and criterion-related validity were used to establish validity. Internal consistency reliability, split-half reliability, and test-retest reliability were used to establish reliability. RESULTS: The final scale contained five dimensions and 24 items, including interpersonal relationship and healthcare strains, worries and concerns about the future, physical appearance and sex strains, daily difficulties and health. The average content validity index of the scale was 0.975. The goodness-of-fit index (χ2/DF = 2.416, RMSEA = 0.057, GFI = 0.896, CFI = 0.947, IFI = 0.947, and TLI = 0.939) indicated that the model was well-fitted. The composite reliability (CR) of the dimensions ranged from 0.825 to 0.934, the average variance extracted (AVE) ranged from 0.539 to 0.712, and the correlation coefficients of each dimension with the other dimensions were less than the square root of the AVE for that dimension. The Criterion-related validity was 0.511. The Cronbach's alpha was 0.938, and the dimensions ranged from 0.779 to 0.900. Split-half reliability was 0.853, with dimensions ranging from 0.761 to 0.892. Test-retest reliability was 0.855. CONCLUSIONS: The Chinese version of the SBCS has good reliability and validity, which can be applied to the assessment of stressors in breast cancer patients in China.


Assuntos
Povo Asiático , Neoplasias da Mama , Psicometria , Feminino , Humanos , Povo Asiático/psicologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , China , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tradução , Estresse Psicológico/diagnóstico
13.
Nano Lett ; 23(16): 7319-7326, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37535017

RESUMO

Reactive oxygen species (ROS) widely participate in a variety of chemical reactions in biological and chemical applications. However, due to the extremely short lifetime of most ROS, conventional ROS-detecting techniques cannot show real-time dynamic changes of ROS-driven chemical reactions and identify the actual role of individual reactive species in these reactions. Herein, using in situ liquid cell TEM complemented by ex situ experiments, we directly visualize ROS-driven rapid etching of Prussian bule (PB) in real time and identify the dominant reactive species in etching processes. The results reveal that highly oxidative •OH is the dominant reactive radical in ROS-driven rapid chemical etching and hollow mesoporous PB nanoparticles can be synthesized on a minute-level time scale via •OH-dominated rapid etching. This work provides insight into ROS-related oxidation, which can continuously improve our understanding of ROS chemistry and make ROS more widely applicable in advanced chemical etching.

14.
Int J Mol Sci ; 25(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38612940

RESUMO

Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.


Assuntos
Condensados Biomoleculares , Transdução de Sinais , Biofísica , Diferenciação Celular , Fenótipo
15.
J Environ Manage ; 366: 121694, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971066

RESUMO

The total organic carbon (OC) from plant litter in riparian zones is an important nutrient source for aquatic organisms and plays a crucial role in the nutrient cycling of river ecosystems. Nevertheless, the total amount of OC in dammed rivers gradually decreases, and the restoration methods are rarely researched. A hypothesis was proposed that the periodic inundation altered the process of OC release from plant litter. To explore the impact of periodic inundation on OC release from litter in the riparian zone, litter bags in situ tests were conducted in the Yalong River. Three inundation treatments were conducted for the test samples, which were NS (never submerged by water), PIS (periodic submerged), and PMS (permanent submerged). Results indicated that the amount of OC released from litters in PIS treatment was about 1.1 times that in PMS treatment, and about 2.1 times that in NS treatment. The average release rate coefficient k of PIS treatment (at mean water level) was the highest (12.8 × 10-4 d-1), followed by PMS treatment (11.0 × 10-4 d-1), and NS treatment (5.6 × 10-4 d-1), which demonstrated that the periodic inundation was critical for OC release. The mean water level was a demarcation line where there was a significant difference in the release of OC in the riparian zone (p < 0.05). Flow velocity alone could account for 84% of the variation in OC release rate, while the flow velocity and inundation duration together could achieve an explanatory degree of 86%. This research can provide a valuable scientific basis for the protection and restoration of river ecosystems, especially for the recovery of OC concentration in dammed rivers.

16.
Arch Orthop Trauma Surg ; 144(2): 583-589, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37898976

RESUMO

PURPOSE: This study was designed to investigate influencing factors of out-of-hospital anticoagulation therapy compliance among patients undergoing major orthopaedic surgeries. METHODS: A cross-sectional, descriptive study was conducted from July 2022 to February 2023 among outpatients who underwent major orthopedic surgery in our hospital. Patients (n = 200) were surveyed using the General Information Questionnaire, the General Self-Efficacy Scale, the Specificity of Medication-Taking Beliefs Scale, and the Morisky Medication Adherence Scale. Factors that influenced patient compliance were also determined using univariate and multivariate regression analyses. RESULTS: One hundred eighty-three valid questionnaires were returned, the compliance with outpatient anticoagulation therapy among patients undergoing major orthopaedic surgeries was good in 56.3% (103/183) of all cases and poor in 43.7% (80/183). Multivariate logistic regression analysis showed that medication duration, adverse effects, self-efficacy and medication beliefs influenced adherence to out-of-hospital anticoagulation therapy in patients undergoing major orthopedic surgery (P < 0.05). CONCLUSIONS: Poor compliance with out-of-hospital anticoagulation therapy in patients undergoing major orthopedic surgery is mainly associated with a long course of medication, adverse reactions, low self-efficacy and low medication beliefs. Healthcare staff should strengthen post-discharge anticoagulation management based on relevant influencing factors to enhance patient compliance.


Assuntos
Procedimentos Ortopédicos , Pacientes Ambulatoriais , Humanos , Adesão à Medicação , Estudos Transversais , Assistência ao Convalescente , Alta do Paciente , Anticoagulantes/uso terapêutico
17.
Angew Chem Int Ed Engl ; 63(21): e202401118, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38433100

RESUMO

Inorganic zeolites have excellent molecular sieving properties, but they are difficult to process into macroscopic structures. In this work, we use metal-organic framework (MOF) glass as substrates to engineer the interface with inorganic zeolites, and then assemble the discrete crystalline zeolite powders into monolithic structures. The zeolites are well dispersed and stabilized within the MOF glass matrix, and the monolith has satisfactory mechanical stabilities for membrane applications. We demonstrate the effective separation performance of the membrane for 1,3-butadiene (C4H6) from other C4 hydrocarbons, which is a crucial and challenging separation in the chemical industry. The membrane achieves a high permeance of C4H6 (693.00±21.83 GPU) and a high selectivity over n-butene, n-butane, isobutene, and isobutane (9.72, 9.94, 10.31, and 11.94, respectively). This strategy opens up new possibilities for developing advanced membrane materials for difficult hydrocarbon separations.

18.
Gut ; 72(5): 996-1006, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36113977

RESUMO

OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.


Assuntos
Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Biomarcadores Tumorais , Neoplasias Pancreáticas
19.
J Cell Physiol ; 238(2): 393-406, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36710714

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a strong stimulant of cardiovascular diseases, affecting one-quarter of the world's population. TBC1 domain family member 25 (TBC1D25) regulates the development of myocardial hypertrophy and cerebral ischemia-reperfusion injury; however, its effect on NAFLD/nonalcoholic steatohepatitis (NASH) has not been reported. In this study, we demonstrated that TBC1D25 expression is upregulated in NASH. TBC1D25 deficiency aggravated hepatic steatosis, inflammation, and fibrosis in NASH. In vitro tests revealed that TBC1D25 overexpression restrained NASH responses. Subsequent mechanistic validation experiments demonstrated that TBC1D25 interfered with NASH progression by inhibiting abnormal lipid accumulation and inflammation. TBC1D25 deficiency significantly promoted NASH occurrence and development. Therefore, TBC1D25 may potentially be used as a clinical therapeutic target for NASH treatment.


Assuntos
Hipercolesterolemia , Hepatopatia Gordurosa não Alcoólica , Hipercolesterolemia/patologia , Inflamação/patologia , Lipídeos , Fígado/metabolismo , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Masculino , Animais , Camundongos
20.
Br J Haematol ; 201(5): 982-994, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36872867

RESUMO

Beta-thalassaemia is an inherited haemoglobin disorder characterised by ineffective erythropoiesis (IE). The detailed pathogenesis of IE remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to examine IE in Th3/+ ß-thalassaemic mice. The results showed that the erythroid group was remarkably expanded, and genes involved in biological processes such as iron metabolism, haeme synthesis, protein folding, and response to heat were significantly upregulated from erythroid progenitors to reticulocytes in ß-thalassaemic mice. In particular, we identified a unique cell population close to reticulocytes, named ThReticulocytes, characterised by a high level of heat shock protein 70 (Hsp70) expression and dysregulation of iron metabolism and haeme synthesis signalling. Treatment of ß-thalassaemic mice with the haeme oxygenase inhibitor tin-mesoporphyrin effectively improved the iron disorder and IE, and the ThReticulocyte population and Hsp70 expression were significantly suppressed. This study revealed in detail the progression of IE at the single-cell level and possibly provided clues to find therapeutic targets in thalassaemia.


Assuntos
Talassemia , Talassemia beta , Camundongos , Animais , Talassemia beta/metabolismo , Eritropoese , Reticulócitos/metabolismo , Ferro/metabolismo
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