Control of CCND1 ubiquitylation by the catalytic SAGA subunit USP22 is essential for cell cycle progression through G1 in cancer cells.

Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the core cell cycle machinery: that is, the deubiquitylation of the G1 cyclin D1 (CCND1). Deubiquitylation by USP22 protects CCND1 from proteasome-mediated degradation and occurs separately from the canonical phosphorylation/ubiquitylation mechanism previously shown to regulate CCND1 stability. We demonstrate that control of CCND1 is a key mechanism by which USP22 mediates its known role in cell cycle progression. Finally, USP22 and CCND1 levels correlate in patient lung and colorectal cancer samples and our preclinical studies indicate that targeting USP22 in combination with CDK inhibitors may offer an approach for treating cancer patients whose tumors exhibit elevated CCND1

Immunotherapy-associated cardiovascular toxicities: insights from preclinical and clinical studies

Immune checkpoint inhibitors (ICIs) have become a widely accepted and effective treatment for various types of solid tumors. Recent studies suggest that cardiovascular immune-related adverse events (irAEs) specifically have an incidence rate ranging from 1.14% to more than 5%. Myocarditis is the most common observed cardiovascular irAE. Others include arrhythmias, pericardial diseases, vasculitis, and a condition resembling takotsubo cardiomyopathy. Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway, and the recently discovered lymphocyte-activation gene 3 (LAG-3) pathway, play a critical role in boosting the body’s natural immune response against cancer cells. While ICIs offer significant benefits in terms of augmenting immune function, they can also give rise to unwanted inflammatory side effects known as irAEs. The occurrence of irAEs can vary in severity, ranging from mild to severe, and can impact the overall clinical efficacy of these agents. This review aims to summarize the underlying mechanisms of cardiovascular irAE from both preclinical and clinical studies for a better understanding of cardiovascular irAE in clinical application

Current Situation of Agricultural Soil Pollution in Jiangsu Province: A Meta-Analysis

In recent years, heavy metal contamination in agricultural soils in Jiangsu Province has attracted more and more attention. However, most studies have been characterized by their small scale, few samples, and short-term monitoring. The overall status and temporal accumulation characteristics of heavy metals have not been fully reflected. Therefore, this paper attempted to provide a comprehensive analysis of the current status of heavy metals and provide accurate information for soil pollution management in Jiangsu Province. This paper collected available data in the literature (1993–2021) on heavy metal-polluted agricultural soils in Jiangsu Province. Based on these available data, the weighted mean values of each heavy metal were obtained by meta-analysis. Then, the ecological risks in soils were evaluated and spatiotemporal variations in the accumulation of heavy metals were explored. In addition, suggestions for pollution prevention and control were made by predicting future heavy metal concentrations. The results showed that Cd and Hg were the major polluting elements in Jiangsu Province. The spatial enrichment of heavy metals followed the pattern of southern > northern > central. Heavy metal concentrations in Nanjing, Suzhou, and Xuzhou should be paid special attention. The ecological risk level of heavy metals in agricultural soils in Jiangsu Province was high, predominantly contributed by Hg and Cd. The accumulation of most heavy metals gradually decreased after 2010, while the opposite happened with Cd. Jiangsu Province should continue to take active pollution control measures in order to maintain the decreasing trend of heavy metal concentrations in farmland soils. This study could provide a scientific and theoretical basis for the development of pollution control and soil remediation measures

Current Situation of Agricultural Soil Pollution in Jiangsu Province: A Meta-Analysis

In recent years, heavy metal contamination in agricultural soils in Jiangsu Province has attracted more and more attention. However, most studies have been characterized by their small scale, few samples, and short-term monitoring. The overall status and temporal accumulation characteristics of heavy metals have not been fully reflected. Therefore, this paper attempted to provide a comprehensive analysis of the current status of heavy metals and provide accurate information for soil pollution management in Jiangsu Province. This paper collected available data in the literature (1993–2021) on heavy metal-polluted agricultural soils in Jiangsu Province. Based on these available data, the weighted mean values of each heavy metal were obtained by meta-analysis. Then, the ecological risks in soils were evaluated and spatiotemporal variations in the accumulation of heavy metals were explored. In addition, suggestions for pollution prevention and control were made by predicting future heavy metal concentrations. The results showed that Cd and Hg were the major polluting elements in Jiangsu Province. The spatial enrichment of heavy metals followed the pattern of southern > northern > central. Heavy metal concentrations in Nanjing, Suzhou, and Xuzhou should be paid special attention. The ecological risk level of heavy metals in agricultural soils in Jiangsu Province was high, predominantly contributed by Hg and Cd. The accumulation of most heavy metals gradually decreased after 2010, while the opposite happened with Cd. Jiangsu Province should continue to take active pollution control measures in order to maintain the decreasing trend of heavy metal concentrations in farmland soils. This study could provide a scientific and theoretical basis for the development of pollution control and soil remediation measures

Spatiotemporal Differentiation and Coupling Coordination Relationship of the Production–Living–Ecological Function at County Scale: A Case Study of Jiangsu Province

Land is multifunctional and includes production, living, and ecological functions (PLEF). Each aspect of PLEF is critical to the stability of human and natural ecosystems, and the balanced coordination of the three is an important guarantee of sustainable development. The study of the coupling and coordinated relationship of the three functions is of great significance to comprehensively optimizing the allocation of territorial space and promoting the coordinated and sustainable development of the national territory. Taking Jiangsu as a case study, based on the perspective of PLEF, this research constructed a PLEF evaluation index system adapted to rapidly urbanizing areas at the county scale and adopted the modified coupling coordination degree model (CCDM) for in-depth analyses of their coupling and coordinated relationships. The results of this study showed that the spatial distribution of PLEF had obvious heterogeneity, with living function (L) and ecological function (E) presenting as high in the south and low in the north, and production function (P) presenting as high in the middle and low in the north and south of Jiangsu; from 2010 to 2020, the production function steadily increased, the living function showed obvious signs of improvement, while the ecological function remained basically stable. The coupling degree and coupling coordination degree formed a spatial pattern with the intersection belt of North and Central Jiangsu and Central and South Jiangsu as the high-value area; from 2010 to 2020, both the coupling degree and the coupling coordination degree showed an upward trend. In the future, differentiated development strategies should be implemented according to the law of coupling and coordinated evolution and different regional characteristics. This study will provide a more appropriate reference for promoting the coordinated development of PLEF in rapidly urbanizing areas and formulating county policy planning

Object-aware Video-language Pre-training for Retrieval

Recently, by introducing large-scale dataset and strong transformer network, video-language pre-training has shown great success especially for retrieval. Yet, existing video-language transformer models do not explicitly fine-grained semantic align. In this work, we present Object-aware Transformers, an object-centric approach that extends video-language transformer to incorporate object representations. The key idea is to leverage the bounding boxes and object tags to guide the training process. We evaluate our model on three standard sub-tasks of video-text matching on four widely used benchmarks. We also provide deep analysis and detailed ablation about the proposed method. We show clear improvement in performance across all tasks and datasets considered, demonstrating the value of a model that incorporates object representations into a video-language architecture. The code will be released at \url{https://github.com/FingerRec/OA-Transformer}.Comment: CVPR2022; Code: https://github.com/FingerRec/OA-Transforme

Achiral Sm(III)-Based Metal–Organic Framework as a Luminescence Sensor for Enantiodiscrimination of Quinine and Quinidine

The effective discrimination and determination of the chiral antimalarial drugs quinine (QN) and quinidine (QD) are extremely important for human health. Herein, a 2D achiral Sm-based metal–organic framework (IMU-MOF1 = [Sm(tpba)(L)]n, where Htpba = 4-(2,2′:6″,2′-terpyridin)-4′-ylbenzioc acid and H2L = 2,2′-biquinoline-4,4′-dicarboxylic acid) was successfully prepared by the solvothermal method. More importantly, IMU-MOF1 was designed as an ultrasensitive fluorescent probe for the identification of chiral enantiomer drugs. The limits of detection for QN and QD are 4.24 × 10–11 and 7.54 × 10–12 M, respectively. Furthermore, it was demonstrated that the stronger hydrogen-bonding interactions between IMU-MOF1 and quinine furnish a more efficient energy transfer to the ligands in the sensing process, resulting in a significant fluorescence enhancement of IMU-MOF1

In-Flight Relative Radiometric Calibration of a Wide Field of View Directional Polarimetric Camera Based on the Rayleigh Scattering over Ocean

The directional polarimetric camera (DPC) is a Chinese satellite sensor with a large field of view (FOV) (±50° both along-track and cross-track) and a high spatial resolution (about 3.3 km at nadir) that operates in a sun-synchronous orbit. It is a difficult task to calibrate the in-flight relative radiometric variation of the sensors with such a wide FOV. In this study, a new method based on Rayleigh scattering over the ocean is developed to estimate the radiometric sensitivity variation over the whole FOV of DPC. Firstly, the theoretical uncertainty of the method is analyzed to calibrate the relative radiometric response. The calibration uncertainties are about 2–6.9% (depending on the wavelength) when the view zenith angle (VZA) is 0° and decrease to about 1–3.8% when VZA increases to 70°. Then, the method is applied to evaluate the long-term radiometric drift of the DPC. It is found that the radiometric response of DPC/GaoFen-5 over the whole FOV is progressively drifting over time. The sensitivity at shorter bands decreases more strongly than longer bands, and at the central part of the optics decreases more strongly than the marginal part. During the 14 months (from March 2019 to April 2020) of operational running in-orbit, the DPC radiometric responses of 443 nm, 490 nm, 565 nm, and 670 nm bands drifted by about 4.44–23.08%, 4.75–16.22%, 3.86–9.81%, and 4.7–16.86%, respectively, from the marginal to the central part of the FOV. The radiometric sensitivity has become more stable since January 2020. The monthly radiometric drift is separated into the relative radiometric part and the absolute radiometric part. The relative radiometric drift of DPC is found to be smoothly varying with VZA, which can be parameterized as a polynomial function via VZA. At last, the temporal radiometric drift of DPC/GaoFen-5 is corrected by combining the relative and absolute radiometric coefficients. The correction is convincing by cross calibration with MODIS/Aqua observation over the desert sites and improving the aerosol retrievals. The Rayleigh method in this study is efficient for the radiometric sensitivity calibration of wide FOV satellite sensors