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A rare population of massive disk galaxies have been found to invade the red sequence dominated by early-type galaxies. The formation and origins of these red/quenched massive disk galaxies have recently gained great interest. The quenching mechanisms that are usually proposed, such as bar quenching and environment quenching, do not seem to be suitable for those bulgeless quenched disks in a low-density environment. In this paper, we use the TNG300 simulation to investigate the formation of massive quenched central disk galaxies. It is found that these galaxies contain less gas than their star-forming counterparts and harbor giant super massive black holes (SMBHs; above 108 M ⊙). By tracing their formation history, we found that quenched disk galaxies formed early and preserved disk morphology for cosmological timescales. They have experienced less than one major merger on average, and mini-mergers (mass ratio <1/10) have mainly contributed to the growth of their SMBHs. In the IllustrisTNG simulation, the black hole feedback mode switches from thermal to kinetic feedback when the black hole mass is more massive than ∼108 M ⊙, which is more efficient to eject gas outside of the galaxy and to suppress further cooling of the hot gaseous halo. We conclude that the dominant quenching mechanism in massive red/quenched disk galaxies is kinetic active galactic nuclei feedback.

The computer vision technique has been rapidly adopted in cow lameness detection research due to its noncontact characteristic and moderate price. This paper attempted to summarize the research progress of computer vision in the detection of lameness. Computer vision lameness detection systems are not popular on farms, and the accuracy and applicability still need to be improved. This paper discusses the problems and development prospects of this technique from three aspects: detection methods, verification methods and application implementation. The paper aims to provide the reader with a summary of the literature and the latest advances in the field of computer vision detection of lameness in dairy cows.

Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid β-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and β-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy.

There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis. In addition, we also explored the signatures of TCR repertoires in the cervical tumor tissues and paired sentinel lymph nodes from 16 CC patients and their potential value in predicting the prognosis of patients. Our results revealed that the diversity of circulating TCR repertoire gradually decreased during the cervix carcinogenesis and progression, but the circulating TCR repertoires in CC patients were more similar to CIN patients than healthy women. Interestingly, several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs, which differed from those observed in CIN patients. In addition, the TCR repertoire diversity in sentinel lymphatic nodes from CC patients was higher than in tumor tissues. More importantly, less clonotypes in TCR repertoire of sentinel lymphatic node was associated with the poor prognosis of the patients. Overall, our findings suggested that TCR repertoire might be a potential indicator of immune monitoring and a biomarker for predicting the prognosis of CC patients. Although functional studies of T cell populations are clearly required, this study have expanded our understanding of T cell immunity during the development of CC and provided an experimental basis for further studies on its pathogenesis and immunotherapy.

This research presents a method based on deep learning for the reverse design of sound-absorbing structures. Traditional methods require time-consuming individual numerical simulations followed by cumbersome calculations, whereas the deep learning design method significantly simplifies the design process, achieving efficient and rapid design objectives. By utilizing deep neural networks, a mapping relationship between structural parameters and the sound absorption coefficient curve is established. The forward network predicts the sound absorption coefficient curve, while the reverse network enables the on-demand design of structural parameters for broadband high sound absorption. During the design process, a mean squared error (MSE) below 0.0001 is achieved. The accuracy of the proposed design method is validated through examples. The results demonstrate that the trained deep learning neural network could effectively replace the complex physical mechanisms between structural parameters and sound absorption coefficient curves. This deep learning design method could also be extended to other types of metamaterial reverse designs, significantly enhancing the efficiency of complex metamaterial designs. Lightweight design is crucial for energy saving and emission reduction. With the total mass and average sound absorption coefficient of sound-absorbing materials as targets, the NSGA-II algorithm has been used for multi-objective optimization design. The optimized average sound absorption coefficient increased by 4.84%, and the total material mass was reduced by 18.98%.

Understanding the fluorescence resonance energy transfer (FRET) of metal nanoparticles at the atomic level has long been a challenge due to the lack of accurate systems with definite distance and orientation of molecules. Here we present the realization of achieving FRET between two atomically precise copper nanoclusters through cocrystallization-induced spatial confinement. In this study, we demonstrate the establishment of FRET in a cocrystallized Cu 8 ( p -MBT) 8 (PPh 3 ) 4 @Cu 10 ( p -MBT) 10 (PPh 3 ) 4 system by exploiting the overlapping spectra between the excitation of the Cu 10 ( p -MBT) 10 (PPh 3 ) 4 cluster and the emission of the Cu 8 ( p -MBT) 8 (PPh 3 ) 4 cluster, combined with accurate control over the confined space between the two nanoclusters. Density functional theory is employed to provide deeper insights into the role of the distance and dipole orientations of molecules to illustrate the FRET procedure between two cluster molecules at the electronic structure level. Understanding FRET of metal nanoparticles at the atomic level has long been a challenge. Here, the authors have achieved FRET activity with atomically precise Cu clusters by using a cocrystallisation-induced spatial confinement strategy.

This study investigated associations between cardiometabolic diseases, frailty, and healthcare utilization and expenditure among Chinese older adults. The participants were 5204 community-dwelling adults aged at least 60 years from the China Health and Retirement Longitudinal Study. Five cardiometabolic diseases were assessed including hypertension, dyslipidemia, diabetes, cardiac diseases and stroke. Frailty status was based on five criteria: slowness, weakness, exhaustion, inactivity, and shrinking. Participants were deemed frailty if they met at least three criteria. As the number of cardiometabolic diseases increased, so did the prevalence of frailty, and the proportion of healthcare utilization, including outpatient visit and inpatient visit. Moreover, the total healthcare expenditure and the odds of catastrophic health expenditure were increased with the number of cardiometabolic disorders. After adjusting for covariates, cardiometabolic diseases were positively associated with higher odds of frailty, incurring outpatient and inpatient visit. And individuals with 2 or more cardiometabolic diseases had a higher odds of catastrophic health expenditure than persons with non-cardiometabolic disease. Participants who were frailty were more likely to report higher odds of healthcare utilization. These findings suggest that both cardiometabolic diseases and frailty assessment may improve identification of older adults likely to require costly, extensive healthcare.

Oncolytic viruses offer an in situ vaccination approach to activate tumor-specific T cell responses. However, the upregulation of PD-L1 expression on tumor cells and immune cells leads to tumor resistance to oncolytic immunotherapy. In this study, we generate an engineered oncolytic virus that coexpresses a PD-L1 inhibitor and GM-CSF. We find that the oncolytic virus is able to secrete the PD-L1 inhibitor that systemically binds and inhibits PD-L1 on tumor cells and immune cells. Importantly, the intratumoral injection with the oncolytic virus overcomes PD-L1-mediated immunosuppression during both the priming and effector phases, provokes systemic T cell responses against dominant and subdominant neoantigen epitopes derived from mutations, and leads to an effective rejection of both virus-injected and distant tumors. In summary, this engineered oncolytic virus is able to activate tumor neoantigen-specific T cell responses, providing a potent, individual tumor-specific oncolytic immunotherapy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy. Oncolytic viruses can activate tumor neoantigen-specific T cell responses. However, PD-L1 upregulation on tumor cells and immune cells leads to tumor resistance to this immunotherapy approach. Here, the authors develop an oncolytic virus which expresses both a PD-L1 inhibitor and GM-CSF which allows an improved tumor neoantigen-specific T cell response in preclinical models.

We study the satellite plane problem of the Milky Way (MW) by using the recently published simulation data of TNG50-1. Here, we only consider the satellite plane consisting of the brightest 14 MW satellites (11 classical satellites plus Canes Venatici I, Crater II, and Antlia II). One halo (haloID = 395, at z = 0, hereafter halo395) of 231 MW-like candidates possesses a satellite plane as spatially thin and kinematically coherent as the observed one has been found. Halo395 resembles the MW in a number of intriguing ways: it hosts a spiral central galaxy, and its satellite plane is almost (∼87°) perpendicular to the central stellar disk. In addition, halo395 is embedded in a sheet plane, with a void on the top and bottom, similar to the local environment of MW. More interestingly, we found that 11 of the 14 of the satellites on the plane of halo395 arise precisely from the peculiar geometry of its large-scale environment (e.g., sheet and voids). The remaining three members appeared at the right place with the right velocity by chance at z = 0. Our results support previous studies wherein the satellite plane problem is not seen as a serious challenge to the ΛCDM model and its formation is ascribed to the peculiarities of our environment.