On the identification of N-rich metal-poor field stars with future China space station telescope

During the long term evolution of globular clusters (GCs), a part of member stars are lost to the field. The recently found nitrogen-rich (N-rich) metal-poor field stars are promising candidates of these GC escapees, since N enhancement is the fingerprint of chemically enhanced populations in GCs. In this work, we discuss the possibility of identifying N-rich metal-poor field stars with the upcoming China space station telescope (CSST). We focus on the main survey camera with NUV, u, g, r, i, z, y filters and slitless spectrograph with a resolution about 200. The combination of UV sensitive equipment and prominent N-related molecular lines in the UV band bodes well for the identification: the color-color diagram of (u-g) versus (g-r) is capable of separating N-rich field stars and normal halo stars, if metallicity can be estimated without using the information of u-band photometry. Besides, the synthetic spectra show that a signal-to-noise ratio of 10 is sufficient to identify N-rich field stars. In the near future, a large sample of N-rich field stars found by CSST, combined with state-of-the-art N-body simulations will be crucial to decipher the GC-Galaxy co-evolution.Comment: 13+2 pages, 11+2 figures, 4 tables, accepted by RA

Pre-training of Equivariant Graph Matching Networks with Conformation Flexibility for Drug Binding

The latest biological findings observe that the traditional motionless 'lock-and-key' theory is not generally applicable because the receptor and ligand are constantly moving. Nonetheless, remarkable changes in associated atomic sites and binding pose can provide vital information in understanding the process of drug binding. Based on this mechanism, molecular dynamics (MD) simulations were invented as a useful tool for investigating the dynamic properties of a molecular system. However, the computational expenditure limits the growth and application of protein trajectory-related studies, thus hindering the possibility of supervised learning. To tackle this obstacle, we present a novel spatial-temporal pre-training method based on the modified Equivariant Graph Matching Networks (EGMN), dubbed ProtMD, which has two specially designed self-supervised learning tasks: an atom-level prompt-based denoising generative task and a conformation-level snapshot ordering task to seize the flexibility information inside MD trajectories with very fine temporal resolutions. The ProtMD can grant the encoder network the capacity to capture the time-dependent geometric mobility of conformations along MD trajectories. Two downstream tasks are chosen, i.e., the binding affinity prediction and the ligand efficacy prediction, to verify the effectiveness of ProtMD through linear detection and task-specific fine-tuning. We observe a huge improvement from current state-of-the-art methods, with a decrease of 4.3% in RMSE for the binding affinity problem and an average increase of 13.8% in AUROC and AUPRC for the ligand efficacy problem. The results demonstrate valuable insight into a strong correlation between the magnitude of conformation's motion in the 3D space (i.e., flexibility) and the strength with which the ligand binds with its receptor

The epidemiological patterns of non-Hodgkin lymphoma: global estimates of disease burden, risk factors, and temporal trends

BackgroundThe incidence of non-Hodgkin’s lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally.MethodsThe up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040.ResultsIn 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040.ConclusionIn this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries

Empower the Science of Organ Donation by Multidisciplinary Collaboration

Inter-discipline is formed by the interpenetration and integration of multiple disciplines, which has become a notable trend involving interdisciplinary activities and a combination of research and development. Learned from experience worldwide, the management mode for organ donation and procurement activities varies among countries, but the core of the disciplinary construction of organ donation remains the same. The theoretical basis and practice of organ donation is not purely a matter of coordination, but its ground of knowledge is built upon multidisciplinary integration and its implementation relies on a joint-effort approach and requires collaboration of multiple teams. From the sociological viewpoint, organ donation represents the gift of life for transplant patients, which founds the key element in enhancing the harmony of society. While, from a practical perspective, its professionalism has been widely recognized by the international medical community. As a complex medical and social act, organ donation is a medical-centered subject with sociological, humanistic, ethical, psychologic, and juristic attributes. This chapter will provide an overview of how multidisciplinary collaboration empowers the science of organ donation, followed by the summary of recent efforts taken in China in pursuit of this goal as an example

Accumbal Adenosine A2A Receptors Enhance Cognitive Flexibility by Facilitating Strategy Shifting

The deficits of cognitive flexibility (including attentional set-shifting and reversal learning) concomitant with dysfunction of the striatum are observed in several neuropsychiatric disorders. Rodent and human studies have identified the striatum [particularly the dorsomedial striatum (DMS) and nucleus accumbens (NAc)] as the critical locus for control of cognitive flexibility, but the effective neuromodulator and pharmacological control of cognitive flexibility remains to be determined. The adenosine A2A receptors (A2ARs) are highly enriched in the striatopallidal neurons where they integrate dopamine and glutamate signals to modulate several cognitive behaviors, but their contribution to cognitive flexibility control is unclear. In this study, by coupling an automated operant cognitive flexibility task with striatal subregional knockdown (KD) of the A2AR via the Cre-loxP strategy, we demonstrated that NAc A2AR KD improved cognitive flexibility with enhanced attentional set-shifting and reversal learning by decreasing regressive and perseverative errors, respectively. This facilitation was not attributed to mnemonic process or motor activity as NAc A2AR KD did not affect the visual discrimination, lever-pressing acquisition, and locomotor activity, but was associated with increased attention and motivation as evident by the progressive ratio test (PRT). In contrast to NAc A2ARs, DMS A2ARs KD neither affected visual discrimination nor improved set-shifting nor reversal learning, but promoted the effort-related motivation. Thus, NAc and DMS A2ARs exert dissociable controls of cognitive flexibility with NAc A2ARs KD selectively enhancing cognitive flexibility by facilitating strategy shifting with increased motivation/attention

YOLOv6: A Single-Stage Object Detection Framework for Industrial Applications

For years, the YOLO series has been the de facto industry-level standard for efficient object detection. The YOLO community has prospered overwhelmingly to enrich its use in a multitude of hardware platforms and abundant scenarios. In this technical report, we strive to push its limits to the next level, stepping forward with an unwavering mindset for industry application. Considering the diverse requirements for speed and accuracy in the real environment, we extensively examine the up-to-date object detection advancements either from industry or academia. Specifically, we heavily assimilate ideas from recent network design, training strategies, testing techniques, quantization, and optimization methods. On top of this, we integrate our thoughts and practice to build a suite of deployment-ready networks at various scales to accommodate diversified use cases. With the generous permission of YOLO authors, we name it YOLOv6. We also express our warm welcome to users and contributors for further enhancement. For a glimpse of performance, our YOLOv6-N hits 35.9% AP on the COCO dataset at a throughput of 1234 FPS on an NVIDIA Tesla T4 GPU. YOLOv6-S strikes 43.5% AP at 495 FPS, outperforming other mainstream detectors at the same scale~(YOLOv5-S, YOLOX-S, and PPYOLOE-S). Our quantized version of YOLOv6-S even brings a new state-of-the-art 43.3% AP at 869 FPS. Furthermore, YOLOv6-M/L also achieves better accuracy performance (i.e., 49.5%/52.3%) than other detectors with a similar inference speed. We carefully conducted experiments to validate the effectiveness of each component. Our code is made available at https://github.com/meituan/YOLOv6.Comment: technical repor

High-fat diets enhance and delay ursodeoxycholic acid absorption but elevate circulating hydrophobic bile salts

Background: Ursodeoxycholic acid (UDCA) is a natural drug essential for the treatment of cholestatic liver diseases. The food effects on the absorption of UDCA and the disposition of circulating bile salts remain unclear despite its widespread global uses. This study aims to investigate the effects of high-fat (HF) diets on the pharmacokinetics of UDCA and disclose how the circulated bile salts were simultaneously perturbed.Methods: After an overnight fast, a cohort of 36 healthy subjects received a single oral dose (500 mg) of UDCA capsules, and another cohort of 31 healthy subjects received the same dose after consuming a 900 kcal HF meal. Blood samples were collected from 48 h pre-dose up to 72 h post-dose for pharmacokinetic assessment and bile acid profiling analysis.Results: The HF diets significantly delayed the absorption of UDCA, with the Tmax of UDCA and its major metabolite, glycoursodeoxycholic acid (GUDCA), changing from 3.3 h and 8.0 h in the fasting study to 4.5 h and 10.0 h in the fed study, respectively. The HF diets did not alter the Cmax of UDCA and GUDCA but immediately led to a sharp increase in the plasma levels of endogenous bile salts including those hydrophobic ones. The AUC0–72h of UDCA significantly increased from 25.4 μg h/mL in the fasting study to 30.8 μg h/mL in the fed study, while the AUC0–72h of GUDCA showed no difference in both studies. As a result, the Cmax of total UDCA (the sum of UDCA, GUDCA, and TUDCA) showed a significant elevation, while the AUC0–72h of total UDCA showed a slight increase without significance in the fed study compared to the fasting study.Conclusion: The HF diets delay UDCA absorption due to the extension of gastric empty time. Although UDCA absorption was slightly enhanced by the HF diets, the beneficial effect may be limited in consideration of the simultaneous elevation of circulating hydrophobic bile salts