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1.
Cells ; 13(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38727314

RESUMO

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine was further characterized. One of these, AC027288.3, showed a dramatic increase in the expression of hESF cells undergoing decidualization. When AC027288.3 expression was targeted, the ability of the cells to undergo decidualization as determined by the expression of decidualization marker protein-coding genes was significantly altered. The most affected markers of decidualization whose expression was significantly reduced were FOXO1, FZD4, and INHBA. Therefore, AC027288.3 may be a major upstream regulator of the WNT-FOXO1 pathway and activin-SMAD3 pathways previously shown as critical for hESF decidualization. Finally, we explored possible regulators of AC027288.3 expression during human ESF decidualization. Expression was regulated by cAMP and progesterone. Our results suggest that AC027288.3 plays a role in hESF decidualization and identifies several other lncRNA genes that may also play a role.


Assuntos
Decídua , Endométrio , Fibroblastos , RNA Longo não Codificante , Células Estromais , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fibroblastos/metabolismo , Fibroblastos/citologia , Decídua/metabolismo , Decídua/citologia , Endométrio/citologia , Endométrio/metabolismo , Células Estromais/metabolismo , Células Estromais/citologia , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Gravidez , Adulto , Diferenciação Celular/genética
2.
Sci Rep ; 14(1): 10698, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730235

RESUMO

Janus group-III chalcogenide monolayers and based heterostructures with breaking vertical structural symmetry offer additional prospects in the upcoming high-performance photoelectric devices. We studied the geometrical, electronic, and photoelectric properties of Janus group-III chalcogenide monolayers and heterostructures. The most energy favorable stacking design of ten vertical heterostructures are considered. The results showed that the Janus Se-In-Ga-S and S-In-Ga-Se monolayers exhibit semiconducting characteristics with the band gaps of 1.295 eV and 1.752 eV, respectively. Furthermore, the different stacking configurations and surface termination at interface can realize the transition of band alignment between type I and type II due to the interlayer coupling. Moreover, we systematically investigated the photoelectric properties of Janus group-III chalcogenide heterostructures and predicated an optimized power conversion efficiency of 16.2%. These findings can aid in comprehending the customized characteristics of Janus group-III chalcogenide heterostructures, offering theoretical guidance for creating innovative photoelectric devices.

3.
Sci Bull (Beijing) ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38729801

RESUMO

Two-dimensional (2D) ordered carbon-nitrogen binary compounds (CxNy) show great potential in many fields owing to their diverse structures and outstanding properties. However, the scalable and selective synthesis of 2D CxNy compounds remain a challenge due to the variable C/N stoichiometry induced coexistence of graphitic, pyridinic, and pyrrolic N species and the competitive growth of graphene. Here, this work systematically explored the mechanism of selective growth of a series of 2D ordered CxNy compounds, namely, the g-C3N4, C2N, C3N, and C5N, on various epitaxial substrates via first-principles calculations. By establishing the thermodynamic phase diagram, it is revealed that the individualized surface interaction and symmetry match between 2D CxNy compounds and substrates together enable the selective epitaxial growth of single crystal 2D CxNy compounds within distinct chemical potential windows of feedstock. The kinetics behaviors of the diffusion and attachment of the decomposed feedstock C/N atoms to the growing CxNy clusters further confirmed the feasibility of the substrate mediated selective growth of 2D CxNy compounds. Moreover, the optimal experimental conditions, including the temperature and partial pressure of feedstock, are suggested for the selective growth of targeted 2D CxNy compound on individual epitaxial substrates by carefully considering the chemical potential of carbon/nitrogen as the functional of experimental parameters based on the standard thermochemical tables. This work provides an insightful understanding on the mechanism of selective epitaxial growth of 2D ordered CxNy compounds for guiding the future experimental design.

4.
Inorg Chem ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728855

RESUMO

In this study, new hybrid birefringent crystals of (C8H7N2O2)2[Bi2Br8]·2H2O and (C8H7N2O2)6[Bi2Cl10]Cl2·2H2O were successfully synthesized by introducing a new birefringent group [C8H7N2O2]+ by a simple aqueous solution evaporation method. They crystallize in the P21/n space group, and their structure consists mainly of the π-conjugated group [C8H7N2O2]+ and the octahedron centered on Bi3+. By first-principles calculations, the birefringence response comes from the [C8H7N2O2]+ group with a planar π-conjugated structure. Meanwhile, the synthesis, structure, first-principles calculations, and optical properties are reported in this paper.

5.
Infect Agent Cancer ; 19(1): 21, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693556

RESUMO

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

6.
bioRxiv ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746228

RESUMO

Personalized functional networks (FNs) derived from functional magnetic resonance imaging (fMRI) data are useful for characterizing individual variations in the brain functional topography associated with the brain development, aging, and disorders. To facilitate applications of the personalized FNs with enhanced reliability and reproducibility, we develop an open-source toolbox that is user-friendly, extendable, and includes rigorous quality control (QC), featuring multiple user interfaces (graphics, command line, and a step-by-step guideline) and job-scheduling for high performance computing (HPC) clusters. Particularly, the toolbox, named personalized functional network modeling (pNet), takes fMRI inputs in either volumetric or surface type, ensuring compatibility with multiple fMRI data formats, and computes personalized FNs using two distinct modeling methods: one method optimizes the functional coherence of FNs, while the other enhances their independence. Additionally, the toolbox provides HTML-based reports for QC and visualization of personalized FNs. The toolbox is developed in both MATLAB and Python platforms with a modular design to facilitate extension and modification by users familiar with either programming language. We have evaluated the toolbox on two fMRI datasets and demonstrated its effectiveness and user-friendliness with interactive and scripting examples. pNet is publicly available at https://github.com/MLDataAnalytics/pNet .

7.
ACS Med Chem Lett ; 15(5): 722-730, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38746878

RESUMO

Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors. Drawing on previously described compounds, including GW2580 (4), we have discovered a novel series of compounds based on the imidazo[4,5-b]pyridine scaffold. Initial structure-activity relationship studies culminated in the identification of 36, a lead compound with potent CSF1R biochemical and cellular activity, acceptable in vitro ADME properties, and oral exposure in rat.

8.
Langmuir ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718299

RESUMO

Electrocatalytic reduction (ECR) of CO2 to chemical products is an important carbon emission reduction method. This work uses DFT to study the stability of N-doped graphene-supported four metal single-atom catalysts (M-N-C) and the effects of the coordination environment and metal centers on the selectivity of CO2 ECR to C1 products. The results show that Fe, Co, Ni, and Cu have good stability. The coordination environment has a significant modulating effect on product selectivity, and the change of the number of ligand nitrogen atoms will affect the size of the potential-limiting step of each product. When the number of nitrogen ligands is the same, the different metal centers of the M-N-C catalyst have a significant effect on the selectivity of different products. In addition, the introduction of nitrogen atom ligands can adjust the electronic structure of the graphene-supported metal center, increase the d-band center of most metals, and improve the reaction activity.

9.
J Colloid Interface Sci ; 669: 383-392, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38718591

RESUMO

Phase junctions exhibit great potential in photocatalytic energy conversion, yet the narrow light response region and inefficient charge transfer limit their photocatalytic performance. Herein, an anatase/rutile phase junction modified by plasmonic TiN and oxygen vacancies (TiN/(A-R-TiO2-Ov)) is prepared through an in-situ thermal transformation from TiN for efficient photothermal-assisted photocatalytic hydrogen production for the first time. The content of TiN, oxygen vacancies, and phase components in TiN/(A-R-TiO2-Ov) hybrids can be well-adjusted by tuning the heating time. The as-prepared photocatalysts display a large specific area and wide light absorption due to the synergistic effect of plasmonic excitation, oxygen vacancies, and bandgap excitations. Meanwhile, the multi-interfaces between TiN, anatase, and rutile provide built-in electric fields for efficient separation of photoinduced carriers and hot electron injection via ohmic contact and type-Ⅱ band arrangement. As a result, the TiN/(A-R-TiO2-Ov) photocatalyst shows an excellent photocatalytic hydrogen generation rate of 15.07 mmol/g/h, which is 20.6 times higher than that of titanium dioxide P25. Moreover, temperature-dependent photocatalytic tests reveal that the excellent photothermal conversion caused by plasmonic heating and crystal lattice vibrations in TiN/(A-R-TiO2-Ov) has about 25 % enhancement in photocatalysis (18.84 mmol/g/h). This work provides new inspiration for developing high-performance photocatalysts by optimizing charge transfer and photothermal conversion.

10.
J Am Chem Soc ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722223

RESUMO

Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as ∼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.

11.
Front Plant Sci ; 15: 1372580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736444

RESUMO

The Homeodomain-Leucine Zipper (HD-ZIP) transcription factors play a pivotal role in governing various aspects of plant growth, development, and responses to abiotic stress. Despite the well-established importance of HD-ZIPs in many plants, their functions in Acoraceae, the basal lineage of monocots, remain largely unexplored. Using recently published whole-genome data, we identified 137 putative HD-ZIPs in two Acoraceae species, Acorus gramineus and Acorus calamus. These HD-ZIP genes were further classified into four subfamilies (I, II, III, IV) based on phylogenetic and conserved motif analyses, showcasing notable variations in exon-intron patterns among different subfamilies. Two microRNAs, miR165/166, were found to specifically target HD-ZIP III genes with highly conserved binding sites. Most cis-acting elements identified in the promoter regions of Acoraceae HD-ZIPs are involved in modulating light and phytohormone responsiveness. Furthermore, our study revealed an independent duplication event in Ac. calamus and a one-to-multiple correspondence between HD-ZIP genes of Ac. calamus and Ac. gramineus. Expression profiles obtained from qRT-PCR demonstrated that HD-ZIP I genes are strongly induced by salinity stress, while HD-ZIP II members have contrasting stress responses in two species. HD-ZIP III and IV genes show greater sensitivity in stress-bearing roots. Taken together, these findings contribute valuable insights into the roles of HD-ZIP genes in stress adaptation and plant resilience in basal monocots, illuminating their multifaceted roles in plant growth, development, and response to abiotic stress.

12.
Rev Sci Instrum ; 95(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38739426

RESUMO

With the development of microfluidic technology, microfluidic chips have played a positive role in applications such as cell culture, microfluidic PCR, and nanopore gene sequencing. However, the presence of bubbles interferes with fluid flow and has a significant impact on experimental results. There are many reasons for the generation of bubbles in microfluidic chips, such as pressure changes inside the chip, air vibration inside the chip, and the open chip guiding air into the chip when driving fluid. This study designed and prepared a microfluidic device based on polydimethylsiloxane. First, air was actively introduced into the microfluidic chip, and bubbles were captured through the microfluidic device to simulate the presence of bubbles inside the chip in biological experiments. To remove bubbles trapped in the microfluidic chip, distilled water, distilled water containing surfactants, and mineral oil were pumped into the microfluidic chip. We compared and discussed the bubble removal efficiency under different driving fluids, driving pressures, and open/closed channel configurations. This study helps to understand the mechanism of bubble formation and removal in microfluidic devices, optimize chip structure design and experimental reagent selection, prevent or eliminate bubbles, and reduce the impact of bubbles on experiments.

13.
Ren Fail ; 46(1): 2343818, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38637281

RESUMO

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined. METHODS: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. RESULTS: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs. 46.6%, p < 0.001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality (p = 0.004), need for renal replacement therapy (p = 0.011), and developing stage-3 AKI (p = 0.040) according to the adjusted models. CONCLUSIONS: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.


Assuntos
Injúria Renal Aguda , Neutrófilos , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Prognóstico , Estudos de Coortes , Estudos Retrospectivos , Linfócitos , Injúria Renal Aguda/etiologia
14.
Nat Commun ; 15(1): 3200, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615014

RESUMO

Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1ß, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1ß expression, which thereby alleviate IL-1ß-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.


Assuntos
Histonas , Nefropatias , Humanos , Lisina , Ativação de Macrófagos , Rim , Senescência Celular , Células Epiteliais , Interleucina-1beta , Acetato-CoA Ligase
15.
IEEE Trans Med Imaging ; PP2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656866

RESUMO

Individual brains vary greatly in morphology, connectivity and organization. Individualized brain parcellation is capable of precisely localizing subject-specific functional regions. However, most individualization approaches examined single modality of data and have not generalized to nonhuman primates. The present study proposed a novel multimodal connectivity-based individual parcellation (MCIP) method, which optimizes within-region homogeneity, spatial continuity and similarity to a reference atlas with the fusion of personal functional and anatomical connectivity. Comprehensive evaluation demonstrated that MCIP outperformed state-of-the-art multimodal individualization methods in terms of functional and anatomical homogeneity, predictability of cognitive measures, heritability, reproducibility and generalizability across species. Comparative investigation showed a higher topographic variability in humans than that in macaques. Therefore, MCIP provides improved accurate and reliable mapping of brain functional regions over existing methods at an individual level across species, and could facilitate comparative and translational neuroscience research.

16.
Sci Rep ; 14(1): 9315, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653770

RESUMO

More than 70% of the potash fertilizer globally is produced by the froth flotation process, in which 4-dodecylmorpholine (DMP) serves as a reverse flotation agent. As the potash fertilizer production rapidly rises, the increased DMP levels in discharged brine pose a threat to the production of high-value chemicals. In this paper, composite particles of basic magnesium sulfate@TiO2 (BMS@TiO2) were prepared using a simple and mild loading method. These particles were utilized for the adsorption and photocatalytic degradation of DMP in brine. Compared with normal powdered materials, the granular BMS@TiO2 in this study can be easily separated from liquid, and the degradation intermediates will not enter the brine without causing secondary pollution. BMS@TiO2 consists of 5·1·7 phase (5Mg(OH)2·MgSO4·7H2O) whisker clusters embedding 2.3% TiO2. The adsorption equilibrium of DMP on BMS@TiO2 particles was achieved through hydrogen bonding and pore interception with the adsorption capacity of approximately 5 mg g-1 after 6 h. The photodegradation efficiency of DMP adsorbed on BMS@TiO2 reached about 92% within 16 h, which is compared with that of pure TiO2 nanoparticles. Additionally, excellent stability and recyclability of BMS@TiO2 were also observed in five cycle tests of adsorption and photocatalytic degradation of DMP, and the possible photocatalytic degradation pathways and mechanism of DMP are proposed following molecular electrostatic potential analysis. This work provides a sustainable and environmentally friendly approach for eliminating organic micropollutants from water environments.

17.
Sensors (Basel) ; 24(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38676116

RESUMO

A novel multistatic integrated sensing and communication (ISAC) system based on macro-micro cooperation for the sixth-generation (6G) mobile network is proposed. Instead of using macrosites at both the transmitter and receiver sides, microsites are considered as receivers in cooperative sensing. This system is important since microsites can be deployed more flexibly to reduce their distances to the sensing objects, providing better coverage for sensing service. In this work, we first analyze the deployment problem of microsites, which can be deployed along the radius and azimuth angle to cover macrosite cells. The coverage area of each microsite is derived in terms of its position in the cell. Then, we describe an efficient estimating approach for obtaining the position and velocity of sensing objects in the macrosite cell. By choosing multiple microsites around the targeted sensing area, joint data processing with an efficient optimization method is also provided. Simulation results show that the multistatic ISAC system employing macro-micro cooperation can improve the position and velocity estimation accuracy of objects compared to systems employing macrosite cooperation alone, demonstrating the effectiveness and potential for implementing the proposed system in the 6G mobile network.

18.
Zhen Ci Yan Jiu ; 49(4): 409-414, 2024 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38649210

RESUMO

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.


Assuntos
Pontos de Acupuntura , Pressão Sanguínea , Hipertensão , Estimulação Elétrica Nervosa Transcutânea , Humanos , Hipertensão/terapia , Hipertensão/fisiopatologia
19.
Nat Commun ; 15(1): 3169, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609353

RESUMO

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Ecossistema , Filogeografia , Neoplasias Hepáticas/genética , Perfilação da Expressão Gênica
20.
Mater Today Bio ; 26: 101056, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38660474

RESUMO

Diabetic foot ulcer (DFU) is a highly morbid complication in patients with diabetes mellitus, necessitating the development of innovative pharmaceuticals to address unmet medical needs. Sodium ion (Na+) is a well-established mediator for membrane potential and osmotic equilibrium. Recently, Na+ transporters have been identified as a functional regulator of regeneration. However, the role of Na+ in the intricate healing process of mammalian wounds remains elusive. Here, we found that the skin wounds in hyponatremic mice display a hard-to-heal phenotype. Na+ ionophores that were employed to increase intracellular Na+ content could facilitate keratinocyte proliferation and migration, and promote angiogenesis, exhibiting diverse biological activities. Among of them, monensin A emerges as a promising agent for accelerating the healing dynamics of skin wounds in diabetes. Mechanistically, the elevated mitochondrial Na+ decelerates inner mitochondrial membrane fluidity, instigating the production of reactive oxygen species (ROS), which is identified as a critical effector on the monensin A-induced improvement of wound healing. Concurrently, Na+ ionophores replenish H+ to the mitochondrial matrix, causing an enhancement of mitochondrial energy metabolism to support productive wound healing programs. Our study unfolds a new role of Na+, which is a pivotal determinant in wound healing. Furthermore, it directs a roadmap for developing Na+ ionophores as innovative pharmaceuticals for treating chronic dermal wounds in diabetic patients.

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