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1.
Proc Natl Acad Sci U S A ; 120(13): e2217208120, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36940337

RESUMO

Intercalation-type layered oxides have been widely explored as cathode materials for aqueous zinc-ion batteries (ZIBs). Although high-rate capability has been achieved based on the pillar effect of various intercalants for widening interlayer space, an in-depth understanding of atomic orbital variations induced by intercalants is still unknown. Herein, we design an NH4+-intercalated vanadium oxide (NH4+-V2O5) for high-rate ZIBs, together with deeply investigating the role of the intercalant in terms of atomic orbital. Besides extended layer spacing, our X-ray spectroscopies reveal that the insertion of NH4+ could promote electron transition to 3dxy state of V t2g orbital in V2O5, which significantly accelerates the electron transfer and Zn-ion migration, further verified by DFT calculations. As results, the NH4+-V2O5 electrode delivers a high capacity of 430.0 mA h g-1 at 0.1 A g-1, especially excellent rate capability (101.0 mA h g-1 at 200 C), enabling fast charging within 18 s. Moreover, the reversible V t2g orbital and lattice space variation during cycling are found via ex-situ soft X-ray absorption spectrum and in-situ synchrotron radiation X-ray diffraction, respectively. This work provides an insight at orbital level in advanced cathode materials.

2.
Small ; : e2400099, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507728

RESUMO

Profiting from the unique atomic laminated structure, metallic conductivity, and superior mechanical properties, transition metal carbides and nitrides named MAX phases have shown great potential as anodes in lithium-ion batteries. However, the complexity of MAX configurations poses a challenge. To accelerate such application, a minus integrated crystal orbital Hamilton populations descriptor is innovatively proposed to rapidly evaluate the lithium storage potential of various MAX, along with density functional theory computations. It confirms that surface A-element atoms bound to lithium ions have odds of escaping from MAX. Interestingly, the activated A-element atoms enhance the reversible uptake of lithium ions by MAX anodes through an efficient alloying reaction. As an experimental verification, the charge compensation and SnxLiy phase evolution of designed Zr2SnC MAX with optimized structure is visualized via in situ synchrotron radiation XRD and XAFS technique, which further clarifies the theoretically expected intercalation/alloying hybrid storage mechanism. Notably, Zr2SnC electrodes achieve remarkably 219.8% negative capacity attenuation over 3200 cycles at 1 A g-1. In principle, this work provides a reference for the design and development of advanced MAX electrodes, which is essential to explore diversified applications of the MAX family in specific energy fields.

3.
BMC Cancer ; 24(1): 753, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902711

RESUMO

BACKGROUND: Investigating novel therapeutic strategies for colorectal cancer (CRC) is imperative. However, there is limited research on the use of drugs to target peripheral blood immune cells in this context. To address this gap, we performed a two-sample Mendelian randomization (MR) analysis to identify potential therapeutic targets for CRC. METHODS: We applied two-sample MR to identify the causal relationship between peripheral blood immune cells and CRC. GWAS data were obtained from the IEU OPEN GWAS project. Based on the implications from the MR results, we conducted a comprehensive database search and genetic analysis to explore potential underlying mechanisms. We predicted miRNAs for each gene and employed extensive research for potential therapeutic applications. RESULTS: We have identified causal associations between two peripheral immune cells and colorectal cancer. Activated & resting Treg %CD4 + cell was positively associated with the risks of CRC, while DN (CD4-CD8-) %leukocyte cell exhibited a protective role in tumor progression. NEK7 (NIMA related kinase 7) and LHX9 (LIM homeobox 9) expressed in Treg cells were positively associated with CRC risks and may play a vital role in carcinogenesis. CONCLUSIONS: This study identified causal relationship between peripheral immune cell and CRC. Treg and DN T cells were implicated to own promoting and inhibiting effects on CRC progression respectively. NEK7 and LHX9 in Treg cells were identified as potential biotarget for antitumor therapies.


Assuntos
Neoplasias Colorretais , Análise da Randomização Mendeliana , Linfócitos T Reguladores , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Quinases Relacionadas a NIMA/genética , Fatores de Transcrição/genética
4.
Nano Lett ; 23(18): 8445-8453, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37677143

RESUMO

Tellurium (Te) is an elemental semiconductor with a simple chiral crystal structure. Te in a two-dimensional (2D) form synthesized by a solution-based method shows excellent electrical, optical, and thermal properties. In this work, the chirality of hydrothermally grown 2D Te is identified and analyzed by hot sulfuric acid etching and high-angle tilted high-resolution scanning transmission electron microscopy. The gate-tunable nonlinear electrical responses, including the nonreciprocal electrical transport in the longitudinal direction and the nonlinear planar Hall effect in the transverse direction, are observed in 2D Te under a magnetic field. Moreover, the nonlinear electrical responses have opposite signs in left- and right-handed 2D Te due to the opposite spin polarizations ensured by the chiral symmetry. The fundamental relationship between the spin-orbit coupling and the crystal symmetry in two enantiomers provides a viable platform for realizing chirality-based electronic devices by introducing the degree of freedom of chirality into electron transport.

5.
Exp Mol Pathol ; 128: 104832, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36122795

RESUMO

Stomach adenocarcinoma (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) treatment. Transcriptome, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a Cox regression analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas monocytes, M2 macrophages, eosinophils, and neutrophils were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy in patients with STAD.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Imunoterapia , Microambiente Tumoral/genética
6.
Nano Lett ; 21(18): 7527-7533, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34514803

RESUMO

Tellurium (Te) is a narrow bandgap semiconductor with a unique chiral crystal structure. The topological nature of electrons in the Te conduction band can be studied by realizing n-type doping using atomic layer deposition (ALD) technique on two-dimensional (2D) Te film. In this work, we fabricated and measured the double-gated n-type Te Hall-bar devices, which can operate as two separate or coupled electron layers controlled by the top gate and back gate. Profound Shubnikov-de Haas (SdH) oscillations are observed in both top and bottom electron layers. Landau level hybridization between two layers, compound and charge-transferable bilayer quantum Hall states at filling factor ν = 4, 6, and 8, are analyzed. Our work opens the door for the study of Weyl physics in coupled bilayer systems of 2D materials.

7.
Med Sci Monit ; 26: e929129, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33311428

RESUMO

Liver regeneration (LR) is a set of complicated mechanisms between cells and molecules in which the processes of initiation, maintenance, and termination of liver repair are regulated. Although LR has been studied extensively, there are still numerous challenges in gaining its full understanding. Cells for LR have a wide range of sources and the feature of plasticity, and regeneration patterns are not the same under different conditions. Many patients undergoing partial hepatectomy develop cirrhosis or steatosis. The changes of LR in these cases are not clear. Many types of cells participate in LR. Hepatocytes, biliary epithelial cells, hepatic progenitor cells, and human liver stem cells can serve as the cell sources for LR. However, different types and degrees of damage trigger the response from the most suitable cells. Exploring the cell sources of LR is of great significance for accelerating recovery of liver function under different pathological patterns and developing a cell therapy strategy to cope with the shortage of donors for liver transplantation. In clinical practice, the background of the liver influences regeneration. Fibrosis and steatosis create different LR microenvironments and signal molecule interaction patterns. In addition, factors such as partial hepatectomy, aging, platelets, nerves, hormones, bile acids, and gut microbiota are widely involved in this process. Understanding the influencing factors of LR has practical value for individualized treatment of patients with liver diseases. In this review, we have summarized recent studies and proposed our views. We discuss cell sources and the influential factors on LR to help in solving clinical problems.


Assuntos
Hepatócitos/citologia , Regeneração Hepática/fisiologia , Animais , Microbioma Gastrointestinal , Humanos , Transdução de Sinais , Nicho de Células-Tronco , Células-Tronco/citologia
8.
Med Sci Monit ; 26: e921162, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246704

RESUMO

BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Astragalus propinquus , Humanos , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
9.
Nano Lett ; 19(3): 1955-1962, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30753783

RESUMO

Tellurium (Te) is an intrinsically p-type-doped narrow-band gap semiconductor with an excellent electrical conductivity and low thermal conductivity. Bulk trigonal Te has been theoretically predicted and experimentally demonstrated to be an outstanding thermoelectric material with a high value of thermoelectric figure-of-merit ZT. In view of the recent progress in developing the synthesis route of 2D tellurium thin films as well as the growing trend of exploiting nanostructures as thermoelectric devices, here for the first time, we report the excellent thermoelectric performance of tellurium nanofilms, with a room-temperature power factor of 31.7 µW/cm K2 and ZT value of 0.63. To further enhance the efficiency of harvesting thermoelectric power in nanofilm devices, thermoelectrical current mapping was performed with a laser as a heating source, and we found that high work function metals such as palladium can form rare accumulation-type metal-to-semiconductor contacts to Te, which allows thermoelectrically generated carriers to be collected more efficiently. High-performance thermoelectric Te devices have broad applications as energy harvesting devices or nanoscale Peltier coolers in microsystems.

10.
Nano Lett ; 19(2): 1289-1294, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30673247

RESUMO

The development of van der Waals (vdW) homojunction devices requires materials with narrow bandgaps and simultaneously high hole and electron mobilities for bipolar transport, as well as methods to image and study spatial variations in carrier type and associated conductivity with nanometer spatial resolution. Here, we demonstrate the general capability of near-field scanning microwave microscopy (SMM) to image and study the local carrier type and associated conductivity in operando by studying ambiploar field-effect transistors (FETs) of the 1D vdW material tellurium in 2D form. To quantitatively understand electronic variations across the device, we produce nanometer-resolved maps of the local carrier equivalence backgate voltage. We show that the global device conductivity minimum determined from transport measurements does not arise from uniform carrier neutrality but rather from the continued coexistence of p-type regions at the device edge and n-type regions in the interior of our micrometer-scale devices. This work both underscores and addresses the need to image and understand spatial variations in the electronic properties of nanoscale devices.

11.
Chem Soc Rev ; 47(19): 7203-7212, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30118130

RESUMO

Tellurium (Te) has a trigonal crystal lattice with inherent structural anisotropy. Te is multifunctional, e.g., semiconducting, photoconductive, thermoelectric, piezoelectric, etc., for applications in electronics, sensors, optoelectronics, and energy devices. Due to the inherent structural anisotropy, previously reported synthetic methods predominantly yield one-dimensional (1D) Te nanostructures. Much less is known about 2D Te nanostructures, their processing schemes, and their material properties. This review focuses on the synthesis and morphology control of emerging 2D tellurene and summarizes the latest developments in understanding the fundamental properties of monolayer and few-layer tellurene, as well as the recent advances in demonstrating prototypical tellurene devices. Finally, the prospects for future research and application opportunities as well as the accompanying challenges of 2D tellurene are summarized and highlighted.

12.
Nano Lett ; 18(9): 5760-5767, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30126280

RESUMO

Quantum Hall effect (QHE) is a macroscopic manifestation of quantized states that only occurs in confined two-dimensional electron gas (2DEG) systems. Experimentally, QHE is hosted in high-mobility 2DEG with large external magnetic field at low temperature. Two-dimensional van der Waals materials, such as graphene and black phosphorus, are considered interesting material systems to study quantum transport because they could unveil unique host material properties due to the easy accessibility of monolayer or few-layer thin films at the 2D quantum limit. For the first time, we report direct observation of QHE in a novel low-dimensional material system, tellurene. High-quality 2D tellurene thin films were acquired from recently reported hydrothermal method with high hole mobility of nearly 3000 cm2/(V s) at low temperatures, which allows the observation of well-developed Shubnikov-de Haas (SdH) oscillations and QHE. A four-fold degeneracy of Landau levels in SdH oscillations and QHE was revealed. Quantum oscillations were investigated under different gate biases, tilted magnetic fields, and various temperatures, and the results manifest the inherent information on the electronic structure of Te. Anomalies in both temperature-dependent oscillation amplitudes and transport characteristics were observed that are ascribed to the interplay between the Zeeman effect and spin-orbit coupling, as depicted by the density functional theory calculations.

13.
Nano Lett ; 17(6): 3965-3973, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28562056

RESUMO

Experimental demonstrations of one-dimensional (1D) van der Waals material tellurium (Te) have been presented by Raman spectroscopy under strain and magneto-transport. Raman spectroscopy measurements have been performed under strains along different principle axes. Pronounced strain response along the c-axis is observed due to the strong intrachain covalent bonds, while no strain response is obtained along the a-axis due to the weak interchain van der Waals interaction. Magneto-transport results further verify its anisotropic property, which results in dramatically distinct magneto-resistance behaviors in terms of three different magnetic field directions. Specifically, phase coherence length extracted from weak antilocalization effect, Lϕ ≈ T-0.5, claims its two-dimensional (2D) transport characteristics when an applied magnetic field is perpendicular to the thin film. In contrast, Lϕ ≈ T-0.33 is obtained from universal conductance fluctuations once the magnetic field is along the c-axis of Te, which indicates its nature of 1D transport along the helical atomic chains. Our studies, which are obtained on high quality single crystal Te thin film, appear to serve as strong evidence of its 1D van der Waals structure from experimental perspectives. It is the aim of this paper to address this special concept that differs from the previous well-studied 1D nanowires or 2D van der Waals materials.

14.
Cogn Process ; 18(1): 87-95, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27743143

RESUMO

The estimation of gaze shift has been an important research area in saliency modeling. Gaze movement is a dynamic progress, yet existing estimation methods are limited to estimating scanpaths within only one saliency map, providing results with unsatisfactory accuracy. A bio-inspired method for gaze shift prediction is thus proposed. We take the effect of foveation into account in the proposed model, which plays an important role in the search for dynamic salient regions. The saccadic bias of gaze shifts and the mechanism of inhibition of return in short-term memory are also considered. Based on the probability map derived from these factors, candidates for the next fixation can be randomly generated, and the final scanpath can be acquired point by point. By the evaluation of objective measures, experimental results show that this method possesses better performance in several datasets than many existing models do.


Assuntos
Atenção/fisiologia , Medições dos Movimentos Oculares , Fixação Ocular/fisiologia , Percepção Visual/fisiologia , Adulto , Fóvea Central/fisiologia , Humanos
15.
Chem Sci ; 15(21): 7848-7869, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38817580

RESUMO

In view of the advantages of low cost, environmental sustainability, and high safety, aqueous Zn-ion batteries (AZIBs) are widely expected to hold significant promise and increasingly infiltrate various applications in the near future. The development of AZIBs closely relates to the properties of cathode materials, which depend on their structures and corresponding dynamic evolution processes. Synchrotron radiation light sources, with their rich advanced experimental methods, serve as a comprehensive characterization platform capable of elucidating the intricate microstructure of cathode materials for AZIBs. In this review, we initially examine available cathode materials and discuss effective strategies for structural regulation to boost the storage capability of Zn2+. We then explore the synchrotron radiation techniques for investigating the microstructure of the designed materials, particularly through in situ synchrotron radiation techniques that can track the dynamic evolution process of the structures. Finally, the summary and future prospects for the further development of cathode materials of AZIBs and advanced synchrotron radiation techniques are discussed.

16.
Front Neurosci ; 18: 1346634, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525376

RESUMO

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

17.
ACS Nano ; 18(23): 15107-15113, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38819119

RESUMO

Superconducting-based electronic devices have shown great potential for future quantum computing applications. One key building block device is a superconducting field-effect transistor based on a superconductor-semiconductor-superconductor Josephson-junction (JJ) with a gate-tunable semiconducting channel. However, the performance of such devices is highly dependent on the quality of the superconductor to semiconductor interface. In this study, we present an alternative method to obtain a high-quality interface by using intimate contact. We investigate the proximity-induced superconductivity in chiral crystal tellurium (Te) and fabricate a PdxTe-Te-PdxTe JJ with an ambipolar supercurrent that is gate-tunable and exhibits multiple Andreev reflections. The semiconducting two-dimensional Te single crystal is grown hydrothermally and partially converted to superconducting PdxTe by controlled annealing. Our work demonstrates a promising path for realizing controllable superconducting electronic devices with high-quality superconducting interfaces; thus, we can continue to advance the field of quantum computing and other interface-based technologies.

18.
Small Methods ; 8(7): e2301115, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38145365

RESUMO

Aqueous zinc ion batteries (AZIBs) show great potential in large-scale energy storage systems. However, the inferior cycling life due to water-induced parasitic reactions and uncontrollable dendrites growth impede their application. Electrolyte optimization via the use of additives is a promising strategy to enhance the stability of AZIBs. Nevertheless, the mechanism of optimal multifunctional additive strategy requires further exploration. Herein, sodium dodecyl benzene sulfonate (SDBS) is proposed as a dual-functional additive in ZnSO4 electrolyte. Benefiting from the additive, both side reactions and zinc dendrites growth are significantly inhibited. Further, a synchrotron radiational spectroscopic study is employed to investigate SDB- adjusted electric double layer (EDL) near the Zn surface and the optimized solvation sheath of Zn2+. First-principles calculations verify the firm adsorption of SDB-, and restriction of random diffusion of Zn2+ on the Zn surface. In particular, the SDBS additive endows Zn||Zn symmetric cells with a 1035 h ultra-stable plating/stripping at 0.2 mA cm-2. This work not only provides a promising design strategy by dual-functional electrolyte additives for high stable AZIBs, but also exhibits the prospect of synchrotron radiation spectroscopy analysis on surface EDL and Zn2+ solvation shell optimization.

19.
Cancer Med ; 12(11): 12263-12271, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37039263

RESUMO

AIM: This study was aimed to evaluate the safety and the efficacy of gemcitabine and oxaliplatin (GEMOX) combined with donafenib plus tislelizumab as the first-line treatment for patients with unresectable biliary tract cancer (BTC). METHODS: This is a prospective single-center exploratory study. Eligible patients (Stage III/IV BTC, at least one measurable disease according to RECIST v1.1, etc.) received gemcitabine 1000 mg/m2 IV Q3W, oxaliplatin 100 mg/m2 IV Q3W, donafenib 200 mg PO BID, and tislelizumab 200 mg IV Q3W until disease progression, unacceptable toxicity, or withdrawal of consent whichever occurred first. The primary endpoint was safety and secondary endpoints included disease control rate (DCR), objective response rate (ORR), conversion rate, and overall survival (OS). RESULTS: A total of 13 patients were enrolled. The median follow-up time was 420 days (range 345-487). The median duration of treatment was four cycles (range 1-15). The incidence of ≥Grade 3 treatment-related adverse events (TRAEs) was 53.8% and no Grade 5 TRAE. The most frequent Grade 3-4 TRAEs were rash (4/13, 30.8%), platelet count decreased (2/13, 15.4%), and fatigue (2/13, 15.4%). Tumor response was assessed in eight evaluable patients; ORR was 25.0% (95% CI, 3.2%-65.1%) and DCR 87.5% (95% CI, 47.3%-99.7%). The median PFS was 4.8 months (95% CI, 1.25-NE). Three Stage III patients underwent subsequent surgery with a conversion rate of 23.1%. The median OS was not estimable. CONCLUSIONS: GEMOX combined with donafenib plus tislelizumab as the first-line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Oxaliplatina , Gencitabina , Estudos Prospectivos , Neoplasias do Sistema Biliar/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
20.
Nat Commun ; 14(1): 6269, 2023 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-37805657

RESUMO

The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Metabolismo dos Lipídeos , Fatores de Transcrição/metabolismo
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