Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 761
Filter
1.
Adv Mater ; : e2404626, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825781

ABSTRACT

Van der Waals (vdW) integration enables clean contacts for low-dimensional electronic devices. The limitation remains, however, that an additional tunneling contact resistance occurs, owing to the inherent vdW gap between the metal and the semiconductor. Here we demonstrate from theoretical calculations that stronger non-covalent hydrogen-bonding interactions facilitate electron tunneling and significantly reduce the contact resistance, thus promising to break the limitations of the vdW contact. π-Plane hydrogen-bonding contacts in surface-engineered MXene/carbon nanotube metal/semiconductor heterojunctions are realized, and an anomalous temperature-dependent tunneling resistance is observed. Low-dimensional flexible thin-film transistors integrated by hydrogen-bonding contacts exhibit both excellent flexibility and carrier mobility orders of magnitude higher than their counterparts with vdW contacts. Our strategy demonstrates a scalable solution for realizing high-performance and low-power flexible electronics beyond vdW contacts. This article is protected by copyright. All rights reserved.

2.
Brief Bioinform ; 25(4)2024 May 23.
Article in English | MEDLINE | ID: mdl-38833322

ABSTRACT

Recent advances in tumor molecular subtyping have revolutionized precision oncology, offering novel avenues for patient-specific treatment strategies. However, a comprehensive and independent comparison of these subtyping methodologies remains unexplored. This study introduces 'Themis' (Tumor HEterogeneity analysis on Molecular subtypIng System), an evaluation platform that encapsulates a few representative tumor molecular subtyping methods, including Stemness, Anoikis, Metabolism, and pathway-based classifications, utilizing 38 test datasets curated from The Cancer Genome Atlas (TCGA) and significant studies. Our self-designed quantitative analysis uncovers the relative strengths, limitations, and applicability of each method in different clinical contexts. Crucially, Themis serves as a vital tool in identifying the most appropriate subtyping methods for specific clinical scenarios. It also guides fine-tuning existing subtyping methods to achieve more accurate phenotype-associated results. To demonstrate the practical utility, we apply Themis to a breast cancer dataset, showcasing its efficacy in selecting the most suitable subtyping methods for personalized medicine in various clinical scenarios. This study bridges a crucial gap in cancer research and lays a foundation for future advancements in individualized cancer therapy and patient management.


Subject(s)
Precision Medicine , Humans , Precision Medicine/methods , Neoplasms/genetics , Neoplasms/classification , Neoplasms/therapy , Biomarkers, Tumor/genetics , Computational Biology/methods , Medical Oncology/methods , Breast Neoplasms/genetics , Breast Neoplasms/classification , Breast Neoplasms/therapy , Female
3.
BMJ Open ; 14(5): e083683, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772892

ABSTRACT

OBJECTIVES: This study aims to examine the prevalence of comorbidities in adult patients with psoriasis and compare them with those in control subjects without psoriasis in Tianjin, China. DESIGN: The study is a cross-sectionalanalysis. PARTICIPANTS: The participants were established by identifying all patients (age ≥18 years) who visited hospitals and clinics in Tianjin between 1 January 2016 and 31 October 2019. SETTING: The study group consisted of 20 678 adult patients with psoriasis, and a comparison group was created after 1:1 propensity score matching. Logistic regression analyses were conducted to examine the risk of 22 comorbidities for these two groups. RESULTS: Patients with psoriasis had a significantly higher prevalence of 11 comorbidities and a lower prevalence of 2 comorbidities within 12 months of follow-up. Our results also showed that the proportion of psoriatic arthritis might account for approximately 2% of all patients with psoriasis. This psoriatic arthritis group had a higher average age and CCI (Charlson Comorbidity Index) index score (2.27 >1.62, p <0.001) than the non-arthritis group. CONCLUSIONS: This study showed that psoriasis in Tianjin is associated with various comorbidities. It also emphasises the importance of clinical treatment in improving therapeutic effects and reducing the burden of psoriasis in China.


Subject(s)
Comorbidity , Psoriasis , Humans , Psoriasis/epidemiology , Cross-Sectional Studies , Female , Male , China/epidemiology , Middle Aged , Adult , Prevalence , Arthritis, Psoriatic/epidemiology , Aged , Propensity Score , Databases, Factual , Logistic Models , Case-Control Studies
5.
Foods ; 13(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38731763

ABSTRACT

Ratoon rice, the cultivation of a second crop from the stubble after the main harvest, is recognized as an eco-friendly and resource-saving method for rice production. Here, a field experiment was carried out in the Yangtze River region to investigate the impact of varying stubble heights on the grain quality of ratoon rice, as well as to compare the grain quality between the main and ratoon season. This study, which focused on 12 commonly cultivated rice varieties, conducted a comprehensive analysis assessing milling characteristics, appearance, and cooking quality. The results show that ratoon rice crops exhibited a higher milled rice rate and head rice rate compared to the main rice crops. Conversely, chalky rice percentage, chalkiness degree, and amylose content were lower in ratoon rice crops. Principal component analysis grouped eight relevant quality indicators of rice quality which were concentrated into three categories, with amylose content identified as the key indicator of rice quality for distinguishing between different stubble heights. Random forest results reveal a robust and significant correlation between appearance quality index and amylose content. Subordinate function analysis indicated that a stubble height of 30 cm resulted in optimal rice quality, with Lingliangyou 211 exhibiting the highest quality and Xiangzao Xian 32 the lowest. Overall, our study suggests that ratoon rice crops generally outperform main rice crops in terms of quality, with the optimal measurement at a stubble height of 30 cm. This study holds substantial importance for selecting appropriate stubble heights for ratoon rice crops and enhancing overall rice quality.

6.
Discov Oncol ; 15(1): 156, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733531

ABSTRACT

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

7.
J Transl Med ; 22(1): 458, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750454

ABSTRACT

BACKGROUND: Corneal injuries, often leading to severe vision loss or blindness, have traditionally been treated with the belief that limbal stem cells (LSCs) are essential for repair and homeostasis, while central corneal epithelial cells (CCECs) were thought incapable of such repair. However, our research reveals that CCECs can fully heal and maintain the homeostasis of injured corneas in rats, even without LSCs. We discovered that CXCL14, under PAX6's influence, significantly boosts the stemness, proliferation, and migration of CCECs, facilitating corneal wound healing and homeostasis. This finding introduces CXCL14 as a promising new drug target for corneal injury treatment. METHODS: To investigate the PAX6/CXCL14 regulatory axis's role in CCECs wound healing, we cultured human corneal epithelial cell lines with either increased or decreased expression of PAX6 and CXCL14 using adenovirus transfection in vitro. Techniques such as coimmunoprecipitation, chromatin immunoprecipitation, immunofluorescence staining, western blot, real-time PCR, cell colony formation, and cell cycle analysis were employed to validate the axis's function. In vivo, a rat corneal epithelial injury model was developed to further confirm the PAX6/CXCL14 axis's mechanism in repairing corneal damage and maintaining corneal homeostasis, as well as to assess the potential of CXCL14 protein as a therapeutic agent for corneal injuries. RESULTS: Our study reveals that CCECs naturally express high levels of CXCL14, which is significantly upregulated by PAX6 following corneal damage. We identified SDC1 as CXCL14's receptor, whose engagement activates the NF-κB pathway to stimulate corneal repair by enhancing the stemness, proliferative, and migratory capacities of CCECs. Moreover, our research underscores CXCL14's therapeutic promise for corneal injuries, showing that recombinant CXCL14 effectively accelerates corneal healing in rat models. CONCLUSION: CCECs play a critical and independent role in the repair of corneal injuries and the maintenance of corneal homeostasis, distinct from that of LSCs. The PAX6/CXCL14 regulatory axis is pivotal in this process. Additionally, our research demonstrates that the important function of CXCL14 in corneal repair endows it with the potential to be developed into a novel therapeutic agent for treating corneal injuries.


Subject(s)
Cell Proliferation , Chemokines, CXC , Corneal Injuries , Epithelium, Corneal , PAX6 Transcription Factor , Wound Healing , PAX6 Transcription Factor/metabolism , PAX6 Transcription Factor/genetics , Animals , Corneal Injuries/metabolism , Corneal Injuries/pathology , Humans , Chemokines, CXC/metabolism , Chemokines, CXC/genetics , Epithelium, Corneal/pathology , Epithelium, Corneal/metabolism , Rats, Sprague-Dawley , Epithelial Cells/metabolism , Rats , Cell Movement , Male , Cell Line
8.
Curr Issues Mol Biol ; 46(5): 4004-4020, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38785515

ABSTRACT

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan-Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression.

9.
Metabolites ; 14(5)2024 May 07.
Article in English | MEDLINE | ID: mdl-38786742

ABSTRACT

This study evaluated the differences in the metabolite profile of three n-3 FA fish oil formulations in 12 healthy participants: (1) standard softgels (STD) providing 600 mg n-3 FA; (2) enteric-coated softgels (ENT) providing 600 mg n-3 FA; (3) a new micellar formulation (LMF) providing 374 mg n-3 FA. The pharmacokinetics (PKs), such as the area under the plot of plasma concentration (AUC), and the peak blood concentration (Cmax) of the different FA metabolites including HDHAs, HETEs, HEPEs, RvD1, RvD5, RvE1, and RvE2, were determined over a total period of 24 h. Blood concentrations of EPA (26,920.0 ± 10,021.0 ng/mL·h) were significantly higher with respect to AUC0-24 following LMF treatment vs STD and ENT; when measured incrementally, blood concentrations of total n-3 FAs (EPA/DHA/DPA3) up to 11 times higher were observed for LMF vs STD (iAUC 0-24: 16,150.0 ± 5454.0 vs 1498.9 ± 443.0; p ≤ 0.0001). Significant differences in n-3 metabolites including oxylipins were found between STD and LMF with respect to 12-HEPE, 9-HEPE, 12-HETE, and RvD1; 9-HEPE levels were significantly higher following the STD vs. ENT treatment. Furthermore, within the scope of this study, changes in blood lipid levels (i.e., cholesterol, triglycerides, LDL, and HDL) were monitored in participants for up to 120 h post-treatment; a significant decrease in serum triglycerides was detected in participants (~20%) following the LMF treatment; no significant deviations from the baseline were detected for all the other lipid biomarkers in any of the treatment groups. Despite a lower administered dose, LMF provided higher blood concentrations of n-3 FAs and certain anti-inflammatory n-3 metabolites in human participants-potentially leading to better health outcomes.

10.
Trends Biotechnol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38821834

ABSTRACT

Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy.

11.
J Colloid Interface Sci ; 671: 303-311, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38815367

ABSTRACT

Manganese-based cathodes are competitive candidates for state-of-the-art aqueous zinc-ion batteries (AZIBs) because of their easy preparation method, sufficient nature reserve, and environmental friendliness. However, their poor cycle stability and low rate performance have prevented them from practical applications. In this study, Mn3O4 nanoparticles were formed in situ on the surface and between the interlayers of Ti3C2Tx MXene, which was pretreated by the intercalation of K+ ions. Ti3C2Tx MXene not only provides abundant active sites and high conductivity but also hinders the structural damage of Mn3O4 during charging and discharging. Benefiting from the well-designed K-Ti3C2@Mn3O4 structure, the battery equipped with the K-Ti3C2@Mn3O4 cathode achieved a maximum specific capacity of 312 mAh/g at a current density of 0.3 A/g and carried a specific capacity of approximately 120 mAh/g at a current density of 1 A/g, which remained stable for approximately 500 cycles. The performance surpasses that of most reported Mn3O4-based cathodes. This study pioneers a new approach for building better cathode materials for AZIBs.

12.
Small ; : e2401204, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801305

ABSTRACT

The demand for state-of-the-art high-energy-density lithium-ion batteries is increasing. However, the low specific capacity of electrode materials in conventional full-cell systems cannot meet the requirements. Ni-rich layered oxide cathodes such as Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) have a high theoretical specific capacity of 200 mAh g-1, but it is always accompanied by side reactions on the electrode/electrolyte interface. Phosphorus anode possesses a high theoretical specific capacity of 2596 mAh g-1, but it has a huge volume expansion (≈300%). Herein, a highly compatible and secure electrolyte is reported via introducing an additive with a narrow electrochemical window, Lithium difluoro(oxalato)borate (LiDFOB), into 1 m LiPF6 EC/DMC with tris (2,2,2-trifluoroethyl) phosphate (TFEP) as a cosolvent. LiDFOB participates in the formation of organic/inorganic hybrid electrode/electrolyte interface layers at both the cathode and anode sides. The side reactions on the surface of the NCM811 cathode and the volume expansion of the phosphorus anode are effectively alleviated. The NCM811//RP full cell in this electrolyte shows high capacity retention of 82% after 150 cycles at a 0.5C rate. Meanwhile, the electrolyte shows non-flammability. This work highlights the importance of manipulating the electrode/electrolyte interface layers for the design of lithium-ion batteries with high energy density.

13.
ACS Nano ; 18(22): 14764-14778, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38776362

ABSTRACT

High-energy-density lithium-metal batteries (LMBs) coupling lithium-metal anodes and high-voltage cathodes are hindered by unstable electrode/electrolyte interphases (EEIs), which calls for the rational design of efficient additives. Herein, we analyze the effect of electron structure on the coordination ability and energy levels of the additive, from the aspects of intramolecular electron cloud density and electron delocalization, to reveal its mechanism on solvation structure, redox stability, as-formed EEI chemistry, and electrochemical performances. Furthermore, we propose an electron reconfiguration strategy for molecular engineering of additives, by taking sorbide nitrate (SN) additive as an example. The lone pair electron-rich group enables strong interaction with the Li ion to regulate solvation structure, and intramolecular electron delocalization yields further positive synergistic effects. The strong electron-withdrawing nitrate moiety decreases the electron cloud density of the ether-based backbone, improving the overall oxidation stability and cathode compatibility, anchoring it as a reliable cathode/electrolyte interface (CEI) framework for cathode integrity. In turn, the electron-donating bicyclic-ring-ether backbone breaks the inherent resonance structure of nitrate, facilitating its reducibility to form a N-contained and inorganic Li2O-rich solid electrolyte interface (SEI) for uniform Li deposition. Optimized physicochemical properties and interfacial biaffinity enable significantly improved electrochemical performance. High rate (10 C), low temperature (-25 °C), and long-term stability (2700 h) are achieved, and a 4.5 Ah level Li||NCM811 multilayer pouch cell under harsh conditions is realized with high energy density (462 W h/kg). The proof of concept of this work highlights that the rational ingenious molecular design based on electron structure regulation represents an energetic strategy to modulate the electrolyte and interphase stability, providing a realistic reference for electrolyte innovations and practical LMBs.

14.
Chem Commun (Camb) ; 60(46): 5924-5927, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38757160

ABSTRACT

MUF-15 (MUF = Massey University Framework) is a metal-organic framework with pores that can be tuned by ligand functionalisation. Crystallites of MUF-15 and derivatives were blended with the organic polymer 6FDA-DAM to produce mixed-matrix membranes (MMMs). At a loading of 30 wt%, membranes with MUF-15-F, MUF-15 with an appended fluoro group, exhibited a CO2 permeability of 1300 Barrer and CO2/CH4 selectivity of 37.1. These values surpass membranes with the parent MUF-15 and exceed the Robeson upper bound.

15.
Environ Pollut ; 350: 124005, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38648965

ABSTRACT

Simultaneously stabilizing of arsenic (As) and cadmium (Cd) in co-contaminated soil presents substantial challenges due to their contrasting chemical properties. Schwertmannite (Sch) is recognized as a potent adsorbent for As pollution, with alkali modification showing promising results in the simultaneous immobilization of both As and Cd. This study systematically investigated the long-term stabilization efficacy of alkali-modified Sch in Cd-As co-contaminated farmland soil over a 200-day flooding-drying period. The results revealed that As showed significant mobility in flooded conditions, whereas Cd exhibited increased soil availability under drying phases. The addition of Sch did not affect the trends in soil pH and Eh fluctuations; nonetheless, it led to an augmentation in the levels of amorphous iron oxides and SO42- concentration in soil pore water. At a dosage of 0.5% Sch, there was a notable decrease in the mobility and soil availability of As and Cd under both flooding (34.5% and 53.6% at Day 50) and drying conditions (27.0% and 29.4% at Day 130), primarily promoting the transformation of labile metal(loid) fraction into amorphous iron oxide-bound forms. Throughout the flooding-drying treatment period, Sch maintained stable mineral morphology and mineralogical phase, highlighting its long-term stabilization effect. The findings of this study emphasize the promising application of Sch-based soil remediation agents in mitigating the challenges arising from As-Cd co-contamination. Further research is warranted to explore their application in real farmland settings and their impact on the uptake of toxic metal(loid)s by plants.


Subject(s)
Arsenic , Cadmium , Environmental Restoration and Remediation , Floods , Soil Pollutants , Soil , Arsenic/analysis , Cadmium/analysis , Soil/chemistry , Environmental Restoration and Remediation/methods , Iron Compounds/chemistry , Farms , Adsorption
16.
J Nurs Scholarsh ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654402

ABSTRACT

OBJECTIVE: To investigate the relationship between work readiness and work well-being for newly graduated nurses and the mediating role of emotional labor and psychological capital in this relationship. METHODS: A cross-sectional survey was conducted in mainland China. A total of 478 newly graduated nurses completed the Work Readiness Scale, Emotional Labour Scale, Psychological Capital Questionnaire, and Work Well-being Scale. Descriptive statistical methods, Pearson correlation analysis, and a structural equation model were used to analyze the available data. RESULTS: Newly graduated nurses' work readiness was significantly positively correlated with work well-being (r = 0.21, p < 0.01), deep acting (r = 0.11, p < 0.05), and psychological capital (r = 0.18, p < 0.01). Emotional labor and psychological capital partially mediated the relationship between work readiness and work well-being. Additionally, emotional labor and psychological capital had a chain-mediating effect on the association. CONCLUSIONS AND CLINICAL RELEVANCE: Work readiness not only affects newly graduated nurses' work well-being directly but also indirectly through emotional labor and psychological capital. These results provide theoretical support and guidance for the study and improvement of newly graduated nurses' work well-being and emphasize the importance of intervention measures to improve work readiness and psychological capital and the adoption of deep-acting emotional-labor strategies.

17.
Int J Mol Sci ; 25(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38612546

ABSTRACT

The unsatisfactory efficacy of immunotherapy for colorectal cancer (CRC) remains a major challenge for clinicians and patients. The tumor microenvironment may promote CRC progression by upregulating the expression of hypoxia-inducing factor (HIF) and PD-L1. Therefore, this study explored the expression and correlation of HIF-1α and PD-L1 in the CRC microenvironment. The expression and correlation of HIF-1α and PD-L1 in CRC were analyzed using bioinformatics and Western blotting (WB). The hypoxia and inflammation of the CRC microenvironment were established in the CT26 cell line. CT26 cells were stimulated with two hypoxia mimics, CoCl2 and DFO, which were used to induce the hypoxic environment. Western blotting was used to assess the expression and correlation of HIF-1α and PD-L1 in the hypoxic environment.LPS stimulated CT26 cells to induce the inflammatory environment. WB and bioinformatics were used to assess the expression and correlation of TLR4, HIF-1α, and PD-L1 in the inflammatory environment. Furthermore, the impact of curcumin on the inflammatory environment established by LPS-stimulated CT26 cells was demonstrated through MTT, Transwell, molecular docking, network pharmacology and Western blotting assays. In this study, we found that the HIF-1α/PD-L1 pathway was activated in the hypoxic and inflammatory environment and promoted immune escape in CRC. Meanwhile, curcumin suppressed tumor immune escape by inhibiting the TLR4/HIF-1α/PD-L1 pathway in the inflammatory environment of CRC. These results suggest that combination therapy based on the HIF-1α/PD-L1 pathway can be a promising therapeutic option and that curcumin can be used as a potent immunomodulatory agent in clinical practice.


Subject(s)
Colorectal Neoplasms , Curcumin , Humans , Tumor Microenvironment , B7-H1 Antigen/genetics , Lipopolysaccharides , Molecular Docking Simulation , Toll-Like Receptor 4 , Hypoxia
18.
J Phys Chem Lett ; 15(14): 3929-3937, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38568181

ABSTRACT

Triangulene, as a typical open-shell graphene fragment, has attracted widespread attention for nanospintronics, promising to serve as building blocks in spin-logic units. Here, using ab initio calculations, we systematically study the laser-induced ultrafast spin-dynamic processes on triangulene nanoflakes, decorated with a transition-metal atom. The results reveal a competition between the induced magnetic center and the carbon edge of the triangulene, resulting in the coexistence of dual spin-density-distribution patterns on such single-magnetic-center systems, thus opening up possibilities of complex spin-dynamic scenarios beyond the spin flip. Interestingly, no matter what direction the spin points to, it is possible to achieve reversible spin-transfer processes using the same laser pulse. Increasing the pool of elementary processes to contain not only spin-direction-dependent but also spin-direction-independent scenarios allows for more versatile spin-logic operations, including classical handling of information and quantum computing. In the present work, we suggest downscaling nanospintronic devices by integrating triangulene-based nanostructures.

19.
J Biol Chem ; 300(6): 107311, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38657866

ABSTRACT

The Hippo signaling pathway plays an essential role in organ size control and tumorigenesis. Loss of Hippo signal and hyper-activation of the downstream oncogenic YAP signaling are commonly observed in various types of cancers. We previously identified STRN3-containing PP2A phosphatase as a negative regulator of MST1/2 kinases (i.e., Hippo) in gastric cancer (GC), opening the possibility of selectively targeting the PP2Aa-STRN3-MST1/2 axis to recover Hippo signaling against cancer. Here, we further discovered 1) disulfiram (DSF), an FDA-approved drug, which can similarly block the binding of STRN3 to PP2A core enzyme and 2) CX-6258 (CX), a chemical inhibitor, that can disrupt the interaction between STRN3 and MST1/2, both allowing reactivation of Hippo activity to inhibit GC. More importantly, we found these two compounds, via an MST1/2 kinase-dependent manner, inhibit DNA repair to sensitize GC towards chemotherapy. In addition, we identified thiram, a structural analog of DSF, can function similarly to inhibit cancer cell proliferation or enhance chemotherapy sensitivity. Interestingly, inclusion of copper ion enhanced such effects of DSF and thiram on GC treatment. Overall, this work demonstrated that pharmacological targeting of the PP2Aa-STRN3-MST1/2 axis by drug compounds can potently recover Hippo signal for tumor treatment.

SELECTION OF CITATIONS
SEARCH DETAIL
...