ABSTRACT
Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development.
Subject(s)
Receptor, Fibroblast Growth Factor, Type 1 , Thyroid Cancer, Papillary , Thyroid Neoplasms , YY1 Transcription Factor , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Receptor, Fibroblast Growth Factor, Type 1/genetics , Humans , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Thyroid Neoplasms/genetics , YY1 Transcription Factor/metabolism , YY1 Transcription Factor/genetics , Animals , Cell Line, Tumor , Ubiquitin-Specific Peptidase 7/metabolism , Ubiquitin-Specific Peptidase 7/genetics , Mice , Gene Expression Regulation, Neoplastic , Mice, Nude , Cell Proliferation/physiology , Female , Apoptosis , Cell Movement , MaleABSTRACT
Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.
ABSTRACT
The original load control model of microgrid based on demand response lacks the factors of incentive demand response, the overall satisfaction of users is low, the degree of demand response is low, the Time Of Use (TOU) price of peak-valley filling capacity is weak, and the peak-valley difference of load curve is large. Regarding the limitations of the current microgrid demand response model, this study further optimizes the flexible load control strategy and proposes a two-objective optimization model based on price and incentive. Meanwhile, the model is solved using an improved chaotic particle group algorithm. Finally, the microgrid load data were selected for simulation analysis. The simulation results showed that the comprehensive demand response of flexible control model proposed increased the overall satisfaction of users by 9.51%, the overall operating cost of microgrid suppliers decreased by 12.975/ten thousand yuan, the peak valley difference decreased by 4.61%, and the user demand response increased by 27.24%. The model effectively improves the overall profit of the supply side of the microgrid, improves the user satisfaction, and maximizes the linkage benefits of the supply and demand of the micro grid. In addition, the model effectively reduces the phenomenon of distributed power supply in the microgrid, and realizes the supply and demand matching of the whole load in the microgrid.
ABSTRACT
Moral disengagement is an important aggressive and moral cognition. The mechanisms of changes in moral disengagement remain unclear, especially at the within-person level. We attempted to clarify this by exploring the serial effects of personal relative deprivation and hostility on civic moral disengagement. We conducted a three-wave longitudinal survey with 1058 undergraduates (63.61% women; mean age = 20.97). The results of the random intercept cross-lagged panel model showed that personal relative deprivation at Wave 1 and hostility at Wave 2 formed a serial effect on the within-person changes in civic moral disengagement at Wave 3, and the longitudinal indirect effect test showed that the within-person dynamics in hostility at Wave 2 acted as a mediator. The results of multiple group analysis across genders further showed that the longitudinal indirect role of hostility at Wave 2 was only observed for men, but not for women, which indicates the moderating effect of gender. These findings facilitate an understanding of the mechanisms of aggressive cognitions at the within-person level and offer implications for the prevention and intervention of aggression from the perspective of moral cognition.
Subject(s)
Aggression , Hostility , Morals , Humans , Male , Female , Aggression/psychology , Longitudinal Studies , Young Adult , Adult , Cognition , Social Cognition , Sex FactorsABSTRACT
Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.
ABSTRACT
Bioelectronic devices can be manufactured by organic-inorganic hybrid systems based on biomolecules and silicon semiconductors. The performance of the hybrid systems is largely determined by the adsorption manners of biomolecules on the silicon surface. In this paper, we demonstrated that the X-ray photoelectron spectroscopy (XPS) shake-up satellites and near-edge X-ray absorption fine-structure (NEXAFS) at the carbon K-edges can be used to distinguish the interface of guanine molecules anchored on Si(100) surface. There are only 9 possible stable guanine@Si(100) hybrid systems that have been found based on the density functional theory. According to the characteristic peaks, it is confirmed that NEXAFS spectra are more sensitive to the identification of adsorption configurations. While the first characteristic peak in the low energy region of NEXAFS is capable of distinguishing chemical bonds at the interface of the adsorption configurations. These results may facilitate a better understanding of the interface formations between biomolecules and silicon surfaces, which could be further utilized for the new bioelectronic device design.
ABSTRACT
Polysaccharides derived from diverse sources exhibit distinct rheological and gel properties, exerting a profound impact on their applicability in the food industry. In this study, we collected five Gracilaria chouae samples from distinct geographical regions, namely Rizhao (RZ), Lianyungang (LYG), Ningde (ND), Beihai (BH), and a wild source from Beihai (BHW). We conducted analyses on the chemical composition, viscosity, and rheological properties, as well as gel properties, to investigate the influence of chemical composition on variations in gel properties. The results revealed that the total sugar, sulfate content, and monosaccharide composition of G. chouae polysaccharides exhibit similarity; however, their anhydrogalactose content varies within a range of 15.31% to 18.98%. The molecular weight distribution of G. chouae polysaccharides ranged from 1.85 to 2.09 × 103 kDa. The apparent viscosity of the LYG and BHW polysaccharides was relatively high, whereas that of RZ and ND was comparatively low. The gel strength displayed a similar trend. BHW and LYG exhibited solid-like behavior, while ND, RZ, and BH demonstrated liquid-like characteristics at low frequencies. The redundancy analysis (RDA) analysis revealed a positive correlation between the texture profile analysis (TPA) characteristics and anhydrogalactose. The study could provide recommendations for the diverse applications of G. chouae polysaccharides derived from different geographical regions.
ABSTRACT
The vertical phase distribution of active layers plays a vital role in balancing exciton dissociation and charge transport for achieving efficient polymer solar cells (PSCs). The layer-by-layer (LbL) PSCs are commonly prepared by using sequential spin-coating method from donor and acceptor solutions with distinct solvents and solvent additives. The enhanced exciton dissociation is expected in the LbL PSCs with efficient charge transport in the relatively neat donor or acceptor layers. In this work, a series of LbL all-polymer solar cells (APSCs) were fabricated with PM6 as donor and PY-DT as acceptor, and triplet material m-Ir(CPmPB)3 is deliberately incorporated into PY-DT layer to prolong exciton lifetimes of active layers. The power conversion efficiency (PCE) of LbL APSCs is improved to 18.24% from 17.32% by incorporating 0.3 wt% m-Ir(CPmPB)3 in PY-DT layer, benefiting from the simultaneously enhanced short-circuit current density (JSC) of 25.17 mA cm-2 and fill factor (FF) of 74.70%. The enhancement of PCE is attributed to the efficient energy transfer of m-Ir(CPmPB)3 to PM6 and PY-DT, resulting in the prolonged exciton lifetime in the active layer and the increased exciton diffusion distance. The efficient energy transfer from m-Ir(CPmPB)3 to PM6 and PY-DT layer can be confirmed by the increased photoluminescence (PL) intensity and the prolonged PL lifetime of PM6 and PY-DT in PM6 + m-Ir(CPmPB)3 and PY-DT + m-Ir(CPmPB)3 films. This study indicates that the triplet material as solid additive has great potential in fabricating efficient LbL APSCs by prolonging exciton lifetimes in active layers.
ABSTRACT
Polygalaqii, a new species, is described and illustrated from limestone landform in southern Hunan, China. The new species resembles P.fallax and P.arillata in flower structure of the plants, but readily differs from the latter two in having erect and shorter inflorescences (0.2-1cm VS 10-15cm VS 7-10cm), and fewer flowers (1-5 flowers VS 10-30 flowers VS 10-20 flowers), and the latter two have a later flowering period (late March to mid-April VS May to August VS May to October). And it is an extremely unique new species that will hibernate in the hot summer of July and August. Following the IUCN Red List Criteria, P.qii is assessed as 'Data Deficient (DD)'.
ABSTRACT
A flexible arc-shaped micro-Fiber Bragg Grating (mFBG) array three-dimensional tactile sensor for fingertip signal detection and human pulse monitoring is presented. It is based on a three mFBGs array which is embedded in an arc-shaped poly (dimethylsiloxane) (PDMS) elastomer, which can effectively discriminate the normal force, left force, and right force by monitoring the reflected intensity variation of the three mFBGs. Different from the traditional FBG sensors, this sensor measures force by detecting changes in light intensity, effectively avoiding the wavelength cross-sensitivity impact of temperature variations on the sensor performance. This design strategy simplifies the sensor structure, reduces the system complexity and signal interrogation cost, and enhances reliability and practicality. Through systematic experiments, we successfully validated the sensor's superior performance, achieving a minimum detection force of 0.01 N and providing robust data support for practical applications. In addition, the sensor has been used to monitor human pulse accurately. The successful fabrication and experimental validation of this sensor lay a foundation for its widespread application in fields such as robot perception and human vital signal detection.
ABSTRACT
OBJECTIVE: To develop and validate a nomogram for quantitively predicting lymphovascular invasion (LVI) of breast cancer (BC) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomics and morphological features. METHODS: We retrospectively divided 238 patients with BC into training and validation cohorts. Radiomic features from DCE-MRI were subdivided into A1 and A2, representing the first and second post-contrast images respectively. We utilized the minimal redundancy maximal relevance filter to extract radiomic features, then we employed the least absolute shrinkage and selection operator regression to screen these features and calculate individualized radiomics score (Rad score). Through the application of multivariate logistic regression, we built a prediction nomogram that integrated DCE-MRI radiomics and MR morphological features (MR-MF). The diagnostic capabilities were evaluated by comparing C-indices and calibration curves. RESULTS: The diagnostic efficiency of the A1/A2 radiomics model surpassed that of the A1 and A2 alone. Furthermore, we incorporated the MR-MF (diffusion-weighted imaging rim sign, peritumoral edema) and optimized Radiomics into a hybrid nomogram. The C-indices for the training and validation cohorts were 0.868 (95% CI: 0.839-0.898) and 0.847 (95% CI: 0.787-0.907), respectively, indicating a good level of discrimination. Moreover, the calibration plots demonstrated excellent agreement in the training and validation cohorts, confirming the effectiveness of the calibration. CONCLUSION: This nomogram combined MR-MF and A1/A2 Radiomics has the potential to preoperatively predict LVI in patients with BC.
Subject(s)
Breast Neoplasms , Contrast Media , Magnetic Resonance Imaging , Neoplasm Invasiveness , Nomograms , Radiomics , Adult , Aged , Female , Humans , Middle Aged , Breast/diagnostic imaging , Breast/pathology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Lymphatic Metastasis/diagnostic imaging , Magnetic Resonance Imaging/methods , Neoplasm Invasiveness/diagnostic imaging , Reproducibility of Results , Retrospective StudiesABSTRACT
Extrusion has been proven to be a novel approach for modifying the physicochemical characteristic of Baijiu vinasses (BV) to extract polysaccharides, contributing to the sustainable development of brewing industry. However, the comparison of the bioactivity and bioavailability of extruded (EX) and unextruded (UE) BV polysaccharides was unclear, which impended the determination of the efficacy of extrusion in BV resourcing. In this study, in vitro digestion and fecal fermentation experiments were conducted to investigate the bioavailability, and the results showed that EX exhibited less variation in the monosaccharide composition and molecular weight, while exhibiting a stronger antioxidant capacity compared to UE. Moreover, during fermentation EX increased the abundance of Parasutterella and Lachnospiraceae, while UE promoted the proliferation of Bacteroides, Faecalibacterium, and Dialister, resulting in variation in short-chain fatty acids. These findings indicate that extrusion can enhance the capacity of antioxidants and bioavailability of BV polysaccharides.
ABSTRACT
BACKGROUND AND OBJECTIVES: Peptic ulcer disease (PUD) and post-procedural artificial ulcers are common ulcer disease. For them, Proton pump inhibitor (PPI) and potassium-competitive acid blocker (P-CAB) are commonly used in clinical practice. PPI requires acid, time, and multiple doses, but P-CAB has fewer limitations. We compared the efficacy, safety and prevention of PPI and P-CAB in PUD and artificial ulcer. METHODS: We searched PubMed, ClinicalTrials.gov, Embase, Cochrane Library, and Web of Science databases for all studies. All eligible randomized controlled trials up to August 5, 2023 were included. Healing rates, shrinking rates, treatment-emergent adverse events rates and recurrence rates were measured. Risk of bias, sensitivity analyses, and heterogeneity were also performed. RESULT: 20 researches which were selected from 926 screening studies and in total 6567 participants were included. The risk ratio (RR) of healing rate with P-CABs versus PPIs of PUD at 4-week was RR 1.01 (95% CI 0.98-1.04). In addition, the healing rate distinction of artificial peptic ulcer was RR 1.04 (0.89-1.22), and the shrinking rate was MD 0.10 (-1.30-1.51). The result of TEAEs rate of PUD was RR 1.11 (0.91-1.35) and the delayed bleeding rate of artificial ulcer was RR 0.35 (0.16-0.80). The RR for recurrence rate of drug-related ulcers was 0.45 (0.25-0.81). CONCLUSION: P-CAB is non-inferior in healing artificial ulcer and conventional PUD, also the incidence of TEAEs. But there may be a statistical advantage in holding back delayed bleeding and preventing drug-induced ulcers. More standardized experiments are needed for further applications and more precise conclusions.
ABSTRACT
Weak doping can broaden, shift, and quench plasmon peaks in nanoparticles, but the mechanistic intricacies of the diverse responses to doping remain unclear. In this study, we used the time-dependent density functional theory (TD-DFT) to compute the excitation properties of transition-metal Pd- or Pt-doped gold and silver atomic arrays and investigate the evolution characteristics and response mechanisms of their plasmon peaks. The results demonstrated that the Pd or Pt doping of the off-centered 10 × 2 atomic arrays broadened or shifted the plasmon peaks to varying degrees. In particular, for Pd-doped 10 × 2 Au atomic arrays, the broadened plasmon peak significantly blueshifted, whereas a slight red shift was observed for Pt-doped arrays. For the 10 × 2 Ag atomic arrays, Pd doping caused almost no shift in the plasmon peak, whereas Pt doping caused a substantial red shift in the broadened plasmon peak. The analysis revealed that the diversity in these doping responses was related to the energy positions of the d electrons in the gold and silver atomic clusters and the positions of the doping atomic orbitals in the energy bands. The introduction of doping atoms altered the symmetry and gap size of the occupied and unoccupied orbitals, so multiple modes of single-particle transitions were involved in the excitation. An electron transfer analysis indicated a close correlation between excitation energy and the electron transfer of doping atoms. Finally, the differences in the symmetrically centered 11 × 2 doped atomic array were discussed using electron transfer analysis to validate the reliability of this analytical method. These findings elucidate the microscopic mechanisms of the evolution of plasmon peaks in doped atomic clusters and provide new insights into the rational control and application of plasmons in low-dimensional nanostructures.
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Simultaneous circular dichroism and wavefront manipulation have gained considerable attention in various applications, such as chiroptical spectroscopy, chiral imaging, sorting and detection of enantiomers, and quantum optics, which can improve the miniaturization and integration of the optical system. Typically, structures with n-fold rotational symmetry (n ≥ 3) are used to improve circular dichroism, as they induce stronger interactions between the electric and magnetic fields. However, manipulating the wavefront with these structures remains challenging because they are commonly considered isotropic and lack a geometric phase response in linear optics. Here, we propose and experimentally demonstrate an approach to achieve simultaneous circular dichroism (with a maximum value of â¼0.62) and wavefront manipulation using a plasmonic metasurface made up of C3 Archimedes spiral nanostructures. The circular dichroism arises from the magnetic dipole-dipole resonance and strong interactions between adjacent meta-atoms. As a proof of concept, two metadevices are fabricated and characterized in the near-infrared regime. This configuration possesses the potential for future applications in photodetection, chiroptical spectroscopy, and the customization of linear and nonlinear optical responses.
ABSTRACT
Halogenation of Y-series small-molecule acceptors (Y-SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power-conversion-efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D-structured large π-fused core of guest Y-SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D-conjugated Y-SMAs (X-QTP-4F, including halogen-free H-QTP-4F, chlorinated Cl-QTP-4F, brominated Br-QTP-4F, and iodinated I-QTP-4F) by attaching different halogens into 2D-conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X-QTP-4F, Cl-QTP-4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8-BO host. Moreover, among ternary PM6:L8-BO:X-QTP-4F blends, PM6:L8-BO:Cl-QTP-4F obtains a more uniform and size-suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8-BO:Cl-QTP-4F-based OSCs achieve a 19.0% efficiency, which is among the state-of-the-art OSCs based on 2D-conjugated Y-SMAs and superior to these devices based on PM6:L8-BO host (17.70%) and with guests of H-QTP-4F (18.23%), Br-QTP-4F (18.39%), and I-QTP-4F (17.62%). The work indicates that halogenation in 2D-structured dibenzo[f,h]quinoxaline core of Y-SMAs guests is a promising strategy to gain efficient ternary OSCs.
ABSTRACT
The bidirectional migration of halides and silver causes irreversible chemical corrosion to the electrodes and perovskite layer, affecting long-term operation stability of perovskite solar cells. Here we propose a silver coordination-induced n-doping of [6,6]-phenyl-C61-butyric acid methyl ester strategy to safeguard Ag electrode against corrosion and impede the migration of iodine within the PSCs. Meanwhile, the coordination between DCBP and silver induces n-doping in the PCBM layer, accelerating electron extraction from the perovskite layer. The resultant PSCs demonstrate an efficiency of 26.03% (certified 25.51%) with a minimal non-radiative voltage loss of 126 mV. The PCE of resulting devices retain 95% of their initial value after 2500 h of continuous maximum power point tracking under one-sun irradiation, and > 90% of their initial value even after 1500 h of accelerated aging at 85 °C and 85% relative humidity.
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Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.