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1.
Nature ; 614(7946): 70-74, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36725993

RESUMEN

Strongly interacting spins underlie many intriguing phenomena and applications1-4 ranging from magnetism to quantum information processing. Interacting spins combined with motion show exotic spin transport phenomena, such as superfluidity arising from pairing of spins induced by spin attraction5,6. To understand these complex phenomena, an interacting spin system with high controllability is desired. Quantum spin dynamics have been studied on different platforms with varying capabilities7-13. Here we demonstrate tunable itinerant spin dynamics enabled by dipolar interactions using a gas of potassium-rubidium molecules confined to two-dimensional planes, where a spin-1/2 system is encoded into the molecular rotational levels. The dipolar interaction gives rise to a shift of the rotational transition frequency and a collision-limited Ramsey contrast decay that emerges from the coupled spin and motion. Both the Ising and spin-exchange interactions are precisely tuned by varying the strength and orientation of an electric field, as well as the internal molecular state. This full tunability enables both static and dynamical control of the spin Hamiltonian, allowing reversal of the coherent spin dynamics. Our work establishes an interacting spin platform that allows for exploration of many-body spin dynamics and spin-motion physics using the strong, tunable dipolar interaction.

2.
Nature ; 621(7980): 734-739, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37648865

RESUMEN

Neutral-atom arrays trapped in optical potentials are a powerful platform for studying quantum physics, combining precise single-particle control and detection with a range of tunable entangling interactions1-3. For example, these capabilities have been leveraged for state-of-the-art frequency metrology4,5 as well as microscopic studies of entangled many-particle states6-11. Here we combine these applications to realize spin squeezing-a widely studied operation for producing metrologically useful entanglement-in an optical atomic clock based on a programmable array of interacting optical qubits. In this demonstration of Rydberg-mediated squeezing with a neutral-atom optical clock, we generate states that have almost four decibels of metrological gain. In addition, we perform a synchronous frequency comparison between independent squeezed states and observe a fractional-frequency stability of 1.087(1) × 10-15 at one-second averaging time, which is 1.94(1) decibels below the standard quantum limit and reaches a fractional precision at the 10-17 level during a half-hour measurement. We further leverage the programmable control afforded by optical tweezer arrays to apply local phase shifts to explore spin squeezing in measurements that operate beyond the relative coherence time with the optical local oscillator. The realization of this spin-squeezing protocol in a programmable atom-array clock will enable a wide range of quantum-information-inspired techniques for optimal phase estimation and Heisenberg-limited optical atomic clocks12-16.

3.
Nature ; 602(7897): 420-424, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35173346

RESUMEN

Einstein's theory of general relativity states that clocks at different gravitational potentials tick at different rates relative to lab coordinates-an effect known as the gravitational redshift1. As fundamental probes of space and time, atomic clocks have long served to test this prediction at distance scales from 30 centimetres to thousands of kilometres2-4. Ultimately, clocks will enable the study of the union of general relativity and quantum mechanics once they become sensitive to the finite wavefunction of quantum objects oscillating in curved space-time. Towards this regime, we measure a linear frequency gradient consistent with the gravitational redshift within a single millimetre-scale sample of ultracold strontium. Our result is enabled by improving the fractional frequency measurement uncertainty by more than a factor of 10, now reaching 7.6 × 10-21. This heralds a new regime of clock operation necessitating intra-sample corrections for gravitational perturbations.

4.
Nature ; 588(7837): 239-243, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33299192

RESUMEN

The control of molecules is key to the investigation of quantum phases, in which rich degrees of freedom can be used to encode information and strong interactions can be precisely tuned1. Inelastic losses in molecular collisions2-5, however, have greatly hampered the engineering of low-entropy molecular systems6. So far, the only quantum degenerate gas of molecules has been created via association of two highly degenerate atomic gases7,8. Here we use an external electric field along with optical lattice confinement to create a two-dimensional Fermi gas of spin-polarized potassium-rubidium (KRb) polar molecules, in which elastic, tunable dipolar interactions dominate over all inelastic processes. Direct thermalization among the molecules in the trap leads to efficient dipolar evaporative cooling, yielding a rapid increase in phase-space density. At the onset of quantum degeneracy, we observe the effects of Fermi statistics on the thermodynamics of the molecular gas. These results demonstrate a general strategy for achieving quantum degeneracy in dipolar molecular gases in which strong, long-range and anisotropic dipolar interactions can drive the emergence of exotic many-body phases, such as interlayer pairing and p-wave superfluidity.

5.
Nature ; 588(7838): 408-413, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33328666

RESUMEN

The preparation of large, low-entropy, highly coherent ensembles of identical quantum systems is fundamental for many studies in quantum metrology1, simulation2 and information3. However, the simultaneous realization of these properties remains a central challenge in quantum science across atomic and condensed-matter systems2,4-7. Here we leverage the favourable properties of tweezer-trapped alkaline-earth (strontium-88) atoms8-10, and introduce a hybrid approach to tailoring optical potentials that balances scalability, high-fidelity state preparation, site-resolved readout and preservation of atomic coherence. With this approach, we achieve trapping and optical-clock excited-state lifetimes exceeding 40 seconds in ensembles of approximately 150 atoms. This leads to half-minute-scale atomic coherence on an optical-clock transition, corresponding to quality factors well in excess of 1016. These coherence times and atom numbers reduce the effect of quantum projection noise to a level that is comparable with that of leading atomic systems, which use optical lattices to interrogate many thousands of atoms in parallel11,12. The result is a relative fractional frequency stability of 5.2(3) × 10-17τ-1/2 (where τ is the averaging time in seconds) for synchronous clock comparisons between sub-ensembles within the tweezer array. When further combined with the microscopic control and readout that are available in this system, these results pave the way towards long-lived engineered entanglement on an optical-clock transition13 in tailored atom arrays.

6.
Proc Natl Acad Sci U S A ; 120(35): e2304294120, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37607226

RESUMEN

Simulating the properties of many-body fermionic systems is an outstanding computational challenge relevant to material science, quantum chemistry, and particle physics.-5.4pc]Please note that the spelling of the following author names in the manuscript differs from the spelling provided in the article metadata: D. González-Cuadra, D. Bluvstein, M. Kalinowski, R. Kaubruegger, N. Maskara, P. Naldesi, T. V. Zache, A. M. Kaufman, M. D. Lukin, H. Pichler, B. Vermersch, Jun Ye, and P. Zoller. The spelling provided in the manuscript has been retained; please confirm. Although qubit-based quantum computers can potentially tackle this problem more efficiently than classical devices, encoding nonlocal fermionic statistics introduces an overhead in the required resources, limiting their applicability on near-term architectures. In this work, we present a fermionic quantum processor, where fermionic models are locally encoded in a fermionic register and simulated in a hardware-efficient manner using fermionic gates. We consider in particular fermionic atoms in programmable tweezer arrays and develop different protocols to implement nonlocal gates, guaranteeing Fermi statistics at the hardware level. We use this gate set, together with Rydberg-mediated interaction gates, to find efficient circuit decompositions for digital and variational quantum simulation algorithms, illustrated here for molecular energy estimation. Finally, we consider a combined fermion-qubit architecture, where both the motional and internal degrees of freedom of the atoms are harnessed to efficiently implement quantum phase estimation as well as to simulate lattice gauge theory dynamics.

7.
Proc Natl Acad Sci U S A ; 120(13): e2221874120, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36947515

RESUMEN

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule. It is also a critical player in the regulation of cell size and cell behaviors such as cell aggregation and phototaxis in cyanobacteria, which constitute an important group of prokaryotes for their roles in the ecology and evolution of the Earth. However, c-di-GMP receptors have never been revealed in cyanobacteria. Here, we report the identification of a c-di-GMP receptor, CdgR, from the filamentous cyanobacterium Anabaena PCC 7120. Crystal structural analysis and genetic studies demonstrate that CdgR binds c-di-GMP at the dimer interface and this binding is required for the control of cell size in a c-di-GMP-dependent manner. Different functions of CdgR, in ligand binding and signal transmission, could be separated genetically, allowing us to dissect its molecular signaling functions. The presence of the apo-form of CdgR triggers cell size reduction, consistent with the similar effects observed with a decrease of c-di-GMP levels in cells. Furthermore, we found that CdgR exerts its function by interacting with a global transcription factor DevH, and this interaction was inhibited by c-di-GMP. The lethal effect triggered by conditional depletion of DevH or by the production of several point-mutant proteins of CdgR in cells indicates that this signaling pathway plays critical functions in Anabaena. Our studies revealed a mechanism of c-di-GMP signaling in the control of cell size, an important and complex trait for bacteria. CdgR is highly conserved in cyanobacteria, which will greatly expand our understanding of the roles of c-di-GMP signaling in these organisms.


Asunto(s)
Cianobacterias , Transducción de Señal , Cianobacterias/metabolismo , GMP Cíclico/metabolismo , Regulación de la Expresión Génica , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica
8.
Genomics ; 116(5): 110889, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901654

RESUMEN

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38771132

RESUMEN

The alveolar Type II epithelial (AEC2) cells act as stem cells in the lung for alveolar epithelial maintenance and repair. Chemokine CXCL10 is expressed in injured tissues, modulating multiple cellular functions. AEC2s, previously reported to release chemokines to recruit leukocytes, were found in our study to secrete CXCL10 after bleomycin injury. We found that Sftpc-Cxcl10 transgenic mice were protected from bleomycin injury. The transgenic mice showed an increase in the AEC2 population in the lung by flow cytometry analysis. Both endogenous and exogenous CXCL10 promoted the colony formation efficiency of AEC2s in a 3D organoid growth assay. We identified that the regenerative effect of CXCL10 was CXCR3 independent using Cxcr3-deficient mice, but it was related to the TrkA pathway. Binding experiments showed that CXCL10 interacted with TrkA directly and reversibly. This study demonstrates a previously unidentified AEC2 autocrine signaling of CXCL10 to promote their regeneration and proliferation, probably involving a CXCR3-independent TrkA pathway.

10.
Anal Chem ; 96(1): 394-400, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38149960

RESUMEN

The intercalation capacity of a porous electrode in real batteries is not uniform spatially due to the inevitable structural and compositional inhomogeneity and site-dependent ion and electron transport features. Reliable methods to quantify the capacity distribution are highly desirable but absent so far in battery research. In this paper, a novel optical technique, oblique incident reflection difference (OIRD), was employed to monitor in situ the electrochemical ion (de)intercalation behavior of Prussian blue analogue (PBA) porous films. The OIRD signal responded synchronously to the ion (de)intercalation, and the change in the OIRD signal (ΔI) was positively correlated with the local electrochemical capacity, thereby enabling mapping of the spatially resolved ion storage capacity of the films. Optical analysis further showed that the OIRD response originated from the ion (de)intercalation-induced dielectric constant change of PBA films. This work therefore offers an intriguing in situ and spatially resolved tool for the study of rechargeable batteries.

11.
Mol Genet Genomics ; 299(1): 36, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38492113

RESUMEN

Previous studies have observed relationships between pancreatitis and gut microbiota; however, specific changes in gut microbiota abundance and underlying mechanisms in pancreatitis remain unknown. Metabolites are important for gut microbiota to fulfil their biological functions, and changes in the metabolic and immune environments are closely linked to changes in microbiota abundance. We aimed to clarify the mechanisms of gut-pancreas interactions and explore the possible role of metabolites and the immune system. To this end, we conducted two-sample Mendelian randomisation (MR) analysis to evaluate the casual links between four different types of pancreatitis and gut microbiota, metabolites, and inflammatory cytokines. A two-step MR analysis was conducted to further evaluate the probable mediating pathways involving metabolites and inflammatory cytokines in the causal relationship between pancreatitis and gut microbiota. In total, six potential mediators were identified in the causal relationship between pancreatitis and gut microbiota. Nineteen species of gut microbiota and seven inflammatory cytokines were genetically associated with the four types of pancreatitis. Metabolites involved in glucose and amino acid metabolisms were genetically associated with chronic pancreatitis, and those involved in lipid metabolism were genetically associated with acute pancreatitis. Our study identified alterations in the gut microbiota, metabolites, and inflammatory cytokines in pancreatitis at the genetic level and found six potential mediators of the pancreas-gut axis, which may provide insights into the precise diagnosis of pancreatitis and treatment interventions for gut microbiota to prevent the exacerbation of pancreatitis. Future studies could elucidate the mechanism underlying the association between pancreatitis and the gut microbiota.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Pancreatitis , Humanos , Enfermedad Aguda , Citocinas/genética , Microbioma Gastrointestinal/genética , Estudio de Asociación del Genoma Completo , Pancreatitis/genética , Análisis de la Aleatorización Mendeliana
12.
Small ; 20(14): e2309272, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37988706

RESUMEN

Despite incorporation of organic groups into silica-based aerogels to enhance their mechanical flexibility, the wide temperature reliability of the modified silicone aerogel is inevitably degraded. Therefore, facile synthesis of soft silicone aerogels with wide-temperature stability remains challenging. Herein, novel silicone aerogels containing a high content of Si are reported by using polydimethylvinylsiloxane (PDMVS), a hydrosilylation adduct with water-repellent groups, as a "flexible chain segment" embedded within the aerogel network. The poly(2-dimethoxymethylsilyl)ethylmethylvinylsiloxane (PDEMSEMVS) aerogel is fabricated through a cost-effective ambient temperature/pressure drying process. The optimized aerogel exhibits exceptional performance, such as ultra-low density (50 mg cm-3), wide-temperature mechanical flexibility, and super-hydrophobicity, in comparison to the previous polysiloxane aerogels. A significant reduction in the density of these aerogels is achieved while maintaining a high crosslinking density by synthesizing gel networks with well-defined macromolecules through hydrolytic polycondensation crosslinking of PDEMSEMVS. Notably, the pore/nanoparticle size of aerogels can be fine-tuned by optimizing the gel solvent type. The as-prepared silicone aerogels demonstrate selective absorption, efficient oil-water separation, and excellent thermal insulation properties, showing promising applications in oil/water separation and thermal protection.

13.
Blood ; 139(3): 333-342, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-34665865

RESUMEN

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.


Asunto(s)
Antineoplásicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Rituximab/uso terapéutico , Tretinoina/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Antineoplásicos/administración & dosificación , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab/administración & dosificación , Prevención Secundaria , Tretinoina/administración & dosificación
14.
Opt Express ; 32(3): 3266-3277, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297552

RESUMEN

Low-coherence tunable visible light sources have a wide range of applications in imaging, spectroscopy, medicine, and so on. Second harmonic generation (SHG) based on a superfluorescent fiber source (SFS) can produce high-brightness visible light while retaining most of the characteristics of superfluorescent sources, such as low coherence, low intensity noise and flexible tunability. However, due to the limitations in phase matching conditions, SHG based on SFS is difficult to reach an equilibrium between high efficiency and robustness of phase matching to temperature variation. In this paper, based on a spectral tunable SFS, we provide a comprehensive analysis, both experimental and theoretical, of the impact of wavelength, linewidth, and temperature on the output performance of SHG. Our findings indicate that broader linewidths adversely affect conversion efficiency, yet they enhance the capacity to withstand temperature variations and central wavelength detuning, which is an advantage that traditional SHG methods do not possess. This work may pave the way for utilizing low-coherence visible light in domains and extreme environments where robust output stability becomes imperative.

15.
J Exp Bot ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486360

RESUMEN

Self-incompatibility (SI) is a crucial mechanism that prevents self-fertilization and inbreeding in flowering plants. Citrus exhibits SI regulated by a polymorphic S-locus containing an S-RNase gene and multiple S-locus F-box (SLF) genes. It has been documented that S-RNase functions as the pistil S determinant, but there is no direct evidence that the SLFs closely linked with S-RNase function as pollen S determinants in Citrus. This study assembled the genomes of two pummelo (Citrus grandis) plants and obtained three novel complete and well-annotated S-haplotypes and isolated 36 SLF or SLF-like alleles on the S-loci. Phylogenetic analysis of 138 SLFs revealed that the SLFs were classified into 12 types, including six types with divergent or missing alleles. Furthermore, transformation experiments verified that the conserved S6-SLF7a protein can lead the transition of SI to self-compatibility (SC) by recognizing non-self S8-RNase in 'Mini-Citrus' plants (S7S8 and S8S29, Fortunella hindsii), a model plant for citrus gene function studies. In vitro assays demonstrated interactions between SLFs of different S haplotypes and the Skp1-Cullin1-F-box subunit CgSSK1 protein. This study provides direct evidence that SLF controls the pollen function in Citrus, demonstrating its role in the 'non-self-recognition' SI system.

16.
Opt Lett ; 49(4): 830-833, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38359193

RESUMEN

In a fiber supercontinuum (SC) source, the Raman scattering effect plays a significant role in extending the spectrum into a longer wavelength. Here, by using a phosphorus-doped fiber with a broad Raman gain spectrum as the nonlinear medium, we demonstrate flat SC generation spanning from 850 to 2150 nm. Within the wavelength range of 1.1-2.0 µm, the spectral power density fluctuation is less than 7 dB. Compared to a similar SC source based on a germanium-doped fiber with narrower Raman gain spectrum, the wavelength span is 300 nm broader, and the spectral power density fluctuation is 5 dB lower. This work demonstrates the phosphorus-doped fiber's great advantage in spectrally flat SC generation, which is of great significance in many applications such as optical coherence tomography, absorption spectroscopy, and telecommunication.

17.
Cancer Cell Int ; 24(1): 216, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902704

RESUMEN

Non-small cell lung cancer (NSCLC) is a common and aggressive primary malignancy worldwide. Dysregulation of long non-coding RNAs (lncRNAs) has been shown to play an essential regulatory role in multiple cancers. However, the role of PGM5-AS1 in NSCLC remains unclear. Here, we found that PGM5-AS1 was down-regulated in NSCLC tissues and cells. Furthermore, reduced PGM5-AS1 expression levels were associated with larger tumor size, positive lymph node metastasis, advanced TNM stage and worse prognosis. We found that overexpression of PGM5-AS1 inhibited cell proliferation and metastasis, and induced apoptosis and G0/G1 cell cycle arrest in NSCLC cell lines. Using dual luciferase gene reporter and RNA immunoprecipitation assays, we confirmed that miR-423-5p interacted with PGM5-AS1, and that their expression levels were negatively correlated in NSCLC tissues. miR-423-5p was also found to reverse PGM5-AS1-induced malignant biological behavior. Moreover, we identified slit guidance ligand 2 (SLIT2) as a target gene of miR-423-5p. Using a dual luciferase gene reporter assay, we confirmed the regulatory relationship between SLIT2 and miR-423-5p and demonstrated that their expression levels were negatively correlated. Our rescue experiments showed that SLIT2 knockdown reversed miR-423-5p-mediated effects. Overall, this study identifies PGM5-AS1 as a potential prognostic biomarker for NSCLC and shows that PGM5-AS1 suppresses NSCLC development by regulating the miR-423-5p/SLIT2 axis.

18.
Phys Rev Lett ; 132(19): 190001, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38804927

RESUMEN

Atomic, molecular, and optical (AMO) physics has been at the forefront of the development of quantum science while laying the foundation for modern technology. With the growing capabilities of quantum control of many atoms for engineered many-body states and quantum entanglement, a key question emerges: what critical impact will the second quantum revolution with ubiquitous applications of entanglement bring to bear on fundamental physics? In this Essay, we argue that a compelling long-term vision for fundamental physics and novel applications is to harness the rapid development of quantum information science to define and advance the frontiers of measurement physics, with strong potential for fundamental discoveries. As quantum technologies, such as fault-tolerant quantum computing and entangled quantum sensor networks, become much more advanced than today's realization, we wonder what doors of basic science can these tools unlock. We anticipate that some of the most intriguing and challenging problems, such as quantum aspects of gravity, fundamental symmetries, or new physics beyond the minimal standard model, will be tackled at the emerging quantum measurement frontier. Part of a series of Essays which concisely present author visions for the future of their field.

19.
BMC Cancer ; 24(1): 681, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834966

RESUMEN

BACKGROUND: Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. METHODS: We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. RESULTS: Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. CONCLUSION: Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.


Asunto(s)
Biomarcadores de Tumor , Humanos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Pronóstico , Femenino , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Regulación Neoplásica de la Expresión Génica , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico , Neoplasias/genética , Neoplasias/sangre , Neoplasias/mortalidad , Neoplasias/diagnóstico , Masculino , Biología Computacional/métodos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estimación de Kaplan-Meier , Neoplasias de la Mama/genética , Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/sangre , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias del Colon/genética , Neoplasias del Colon/sangre , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/patología , Neoplasias del Colon/mortalidad , Redes Reguladoras de Genes
20.
Inflamm Res ; 73(6): 961-978, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38587531

RESUMEN

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.


Asunto(s)
Aterosclerosis , Perfilación de la Expresión Génica , Aterosclerosis/genética , Aterosclerosis/inmunología , Animales , Mapas de Interacción de Proteínas/genética , Transcriptoma , Humanos , Biología Computacional , Masculino , Piroptosis/genética , Ratones
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