Serum YKL-40 in coronary heart disease: linkage with inflammatory cytokines, artery stenosis, and optimal cut-off value for estimating major adverse cardiovascular events

ObjectiveYKL-40, previously known as chitinase-3-like protein 1 (CHI3L1), is an inflammation-related glycoprotein that promotes atherosclerosis, but its application and optimal cut-off value as a prognostic biomarker in coronary heart disease (CHD) require more clinical evidence. Thus, this prospective study aimed to evaluate the linkage of serum YKL-40 with disease features, inflammatory cytokines, and major adverse cardiovascular events (MACEs) in CHD patients.MethodsA total of 410 CHD patients were enrolled for serum YKL-40 determination via enzyme-linked immunosorbent assay. Meanwhile, serum YKL-40 levels in 100 healthy controls (HCs) were also quantified.ResultsYKL-40 level was higher in CHD patients compared with that in HCs (P < 0.001). YKL-40 was positively linked with hyperlipidemia (P = 0.014), diabetes mellitus (P = 0.001), fasting blood glucose (P = 0.045), C-reactive protein (P < 0.001), the Gensini score (P < 0.001), and stenosis degree (graded by the Gensini score) (P < 0.001) in CHD patients. In addition, an elevated YKL-40 level was associated with increased levels of tumor necrosis factor alpha (P = 0.001), interleukin (IL)-1β (P = 0.001), IL-6 (P < 0.001), and IL-17A (P = 0.002) in CHD patients. The 1-/2-/3-year cumulative MACE rates of CHD patients were 5.5%, 14.4%, and 25.0%, respectively. Regarding the prognostic capability, YKL-40 ≥100 ng/ml (the median cut-off value) (P = 0.003) and YKL-40 ≥150 ng/ml (the third interquartile cut-off value) (P = 0.021) reflected an elevated accumulating MACE rate, whereas accumulating MACE was not different between CHD patients with YKL-40 ≥80 and <80 ng/ml (the first interquartile cut-off value) (P = 0.083).ConclusionSerum YKL-40 is positively linked with inflammatory cytokines and the Gensini score, whose high expression cut-off by 100 and 150 ng/ml estimates a higher MACE risk in CHD patients

Vision-Language Foundation Models as Effective Robot Imitators

Recent progress in vision language foundation models has shown their ability to understand multimodal data and resolve complicated vision language tasks, including robotics manipulation. We seek a straightforward way of making use of existing vision-language models (VLMs) with simple fine-tuning on robotics data. To this end, we derive a simple and novel vision-language manipulation framework, dubbed RoboFlamingo, built upon the open-source VLMs, OpenFlamingo. Unlike prior works, RoboFlamingo utilizes pre-trained VLMs for single-step vision-language comprehension, models sequential history information with an explicit policy head, and is slightly fine-tuned by imitation learning only on language-conditioned manipulation datasets. Such a decomposition provides RoboFlamingo the flexibility for open-loop control and deployment on low-performance platforms. By exceeding the state-of-the-art performance with a large margin on the tested benchmark, we show RoboFlamingo can be an effective and competitive alternative to adapt VLMs to robot control. Our extensive experimental results also reveal several interesting conclusions regarding the behavior of different pre-trained VLMs on manipulation tasks. We believe RoboFlamingo has the potential to be a cost-effective and easy-to-use solution for robotics manipulation, empowering everyone with the ability to fine-tune their own robotics policy.Comment: Fix typos. Project page: https://roboflamingo.github.i

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

BackgroundCancer-associated fibroblasts (CAFs) are vital components of prominent cellular components in lower-grade gliomas (LGGs) that contribute to LGGs’ progression, treatment resistance, and immunosuppression. Epigenetic modification and immunity have significant implications for tumorigenesis and development.MethodsWe combined aberrant methylation and CAFs abundances to build a prognostic model and the impact on the biological properties of LGGs. Grouping based on the median CAFs abundances score of samples in the TCGA-LGGs dataset, differentially expressed genes and aberrantly methylated genes were combined for subsequent analysis.ResultsWe identified five differentially methylated and expressed genes (LAT32, SWAP70, GSAP, EMP3, and SLC2A10) and established a prognostic gene signature validated in the CGGA-LGGs dataset. Immunohistochemistry (IHC) and in vitro tests were performed to verify these expressions. The high-risk group increased in tumor-promoting immune cells and tumor mutational burden. Notably, risk stratification had different ICB sensitivities in LGGs, and there were also significant sensitivity differences for temozolomide and the other three novel chemotherapeutic agents.ConclusionOur study reveals characteristics of CAFs in LGGs, refines the direct link between epigenetics and tumor stroma, and might provide clinical implications for guiding tailored anti-CAFs therapy in combination with immunotherapy for LGGs patients

Stromal protein CCN family contributes to the poor prognosis in lower-grade gioma by modulating immunity, matrix, stemness, and metabolism

Background: The CCN family of stromal proteins is involved in the regulation of many important biological functions. However, the role of dysregulated CCN proteins in lower-grade glioma (LGG) remain less understand.Methods: The clinical significance of the CCN proteins was explored based on RNA-seq profiles from multiple cohorts. A CCNScore was constructed using LASSO regression analysis. The PanCanAtlas data and MEXPRESS database were employed to elucidate molecular underpinnings.Results: The expression of CCN4 was associated with poor prognosis in LGG. The CCNScore (CCN1 = 0.06, CCN4 = 0.86) showed implication in prognosis prediction, subtype assessment and therapy selection. The gene mutation pattern of the high-CCNScore group was similar with glioblastoma, including EGFR, PTEN, and NF1 mutation frequently. Besides, the high-CCNScore group was comprised of samples mainly classic-like and mesenchymal-like, had lower methylation levels, higher stemness, higher inflammation, higher levels of extracellular matrix remodel and dysfunction of metabolic pathways. On the other hand, the low-CCNScore group consisted mainly of IDH-mutation LGG, and was characterized by TP53, CIC, and ATRX gene mutations, hyper-methylation status, lower stemness, lower proliferation, immune quietness and low extracellular matrix stiffness.Conclusion: In summary, these results outlined the role of CCN family in LGG and provided a potential and promising therapeutic target

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Effect of Bicarbonate Stress on Carbonic Anhydrase Gene Expressions from Orychophragmus violaceus and Brassica juncea seedlings

Three beta-type genes coding for carbonic anhydrase and CA activities from Orychophragmus violaceus L. and Brassica juncea L. leaves in response to NaHCO3-induced bicarbonate stress were examined. Three full-length cDNA CDS sequences were designated as OvCA1, OvCA3, and OvCA4 in Orychophragmus violaceus, and as BjCA1, BjCA3, and BjCA4 in Brassica juncea; these genes encoding beta-CAs were identified and characterized. In particular, OvCA1 and BjCA1 encode two putative chloroplast isoforms. OvCA3 and BjCA3 encode two putative cytosolic isoforms. OvCA4 and BjCA4 encode two putative plasma membrane isoforms. Quantitative real-time RT-PCR analysis revealed that OvCA1 and OvCA4 expressions in Orychophragmus violaceus, BjCA1, and BjCA4 expressions in Brassica juncea changed synchronously with CA activities as bicarbonate stress was intensified. Bicarbonate stress synchronously stimulated OvCA1 and OvCA4 expressions along with CA activities in Orychophragmus violaceus at slight stress level; but it decreased CA activity, BjCA1 and BjCA4 expressions, and stimulated BjCA3 expression in Brassica juncea. Orychoophragmus violaceus could better adapt to slight bicarbonate stress than Brassica juncea due to the former exhibiting higher OvCA3 expression levels and CA activities than the latter. The responses of CA1 and CA4 in Orychophragmus violaceus and CA3 in Brassica juncea to bicarbonate stress partly regulate HCO3- to water and CO 2 supplied to plants. Diverse CA gene expressions can partially account for different adaptation strategies of the two plant species subjected to different bicarbonate stress levels

Differential contributions of NO3-/NH4+ to nitrogen use in response to a variable inorganic nitrogen supply in plantlets of two Brassicaceae species in vitro

BackgroundThe primary sources of nitrogen for plants have been suggested to be nitrate (NO3-) and ammonium (NH4+). However, when both nitrate and ammonium are simultaneously available to plants, it is very difficult to differentially quantify NO3-/NH4+ utilization in culture media or soil. Consequently, the contribution of NO3-/NH4+ to total inorganic nitrogen assimilation cannot be determined.ResultsWe developed a method called the bidirectional stable nitrogen isotope tracer to differentially quantify the nitrate and ammonium utilization by Orychophragmus violaceus (Ov) and Brassica napus (Bn) plantlets in vitro. The utilization efficiency of nitrate was markedly lower than the utilization efficiency of ammonium for plantlets of both Ov and Bn. In both Ov and Bn, the proportion of NO3-/NH4+ utilization did not show a linear relationship with inorganic nitrogen supply. The Ov plantlets assimilated more nitrate than the Bn plantlets at the lowest inorganic nitrogen concentration.ConclusionsQuantifying the utilization of nitrate and ammonium can reveal the differences in nitrate and ammonium assimilation among plants at different inorganic nitrogen supply levels and provide an alternate way to conveniently optimize the supply of inorganic nitrogen in culture media