Serum lactate dehydrogenase activities as systems biomarkers for 48 types of human diseases

Most human diseases are systems diseases, and systems biomarkers are better fitted for diagnostic, prognostic, and treatment monitoring purposes. To search for systems biomarker candidates, lactate dehydrogenase (LDH), a housekeeping protein expressed in all living cells, was investigated. To this end, we analyzed the serum LDH activities from 172,933 patients with 48 clinically defined diseases and 9528 healthy individuals. Based on the median values, we found that 46 out of 48 diseases, leading by acute myocardial infarction, had significantly increased (p  0.8) for hepatic encephalopathy and lung fibrosis

Involvement of TNF-alpha and IL-10 in breast cancer and patient survival

Purpose: To investigate the involvement of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) in the pathogenesis of breast cancer in vivo as well as the activity of ten Chinese herbal compounds in human breast cancer (MCF-7) cell proliferation in vitro.Methods: In the in vivo study, the association of serum TNF-α and IL-10 with breast cancer cell invasiveness and prognosis was determined in female patients (n = 192) with breast cancer, while in the in vitro study, ten herbal Chinese compounds were screened for their effectiveness against MCF-7 cells. The levels of TNF-α, IL-10, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) were assayed using their respective enzyme-linked immunosorbent assay (ELISA) kits. Molecular docking was used to determine the lead compound(s) that can effectively inhibit TNF-α and IL-10.Results: Raised serum levels of TNF-α and IL-10 were significantly associated with breast cancer cell invasiveness and poor prognosis (p < 0.05). Moreover, there was a strong association between breast cancer prognosis and the expression levels of ER, PR and HER2/neu. Serum TNF-α and IL-10 levels were significantly elevated in stages II and III patients and in those with lymph node metastasis. Treatment of MCF-7 cells with the herbal compounds significantly reduced the synthesis and release of TNF-α and IL-10 (p < 0.05). The results of molecular docking showed that baicalein and oridonin significantly inhibited TNF- α and IL-10. The two herbal compounds had the highest docking scores for inhibition of cytokines, as well as favorable interaction energies.Conclusion: These results indicate that TNF-α and IL-10 are involved in the pathogenesis of breast cancer, and that baicalein and oridonin effectively inhibit the proliferation of the cells. Keywords: Baicalein, Breast cancer, Interleukin 10, Oridonin, Tumor necrosis factor alph

Bring Metric Functions into Diffusion Models

We introduce a Cascaded Diffusion Model (Cas-DM) that improves a Denoising Diffusion Probabilistic Model (DDPM) by effectively incorporating additional metric functions in training. Metric functions such as the LPIPS loss have been proven highly effective in consistency models derived from the score matching. However, for the diffusion counterparts, the methodology and efficacy of adding extra metric functions remain unclear. One major challenge is the mismatch between the noise predicted by a DDPM at each step and the desired clean image that the metric function works well on. To address this problem, we propose Cas-DM, a network architecture that cascades two network modules to effectively apply metric functions to the diffusion model training. The first module, similar to a standard DDPM, learns to predict the added noise and is unaffected by the metric function. The second cascaded module learns to predict the clean image, thereby facilitating the metric function computation. Experiment results show that the proposed diffusion model backbone enables the effective use of the LPIPS loss, leading to state-of-the-art image quality (FID, sFID, IS) on various established benchmarks

Extensive tRNA gene changes in synthetic Brassica napus

Allopolyploidization, where two species come together to form a new species, plays a major role in speciation and genome evolution. Transfer RNAs (abbreviated tRNA) are typically 73-94 nucleotides in length, and are indispensable in protein synthesis, transferring amino acids to the cell protein synthesis machinery (ribosome). To date, the regularity and function of tRNA gene sequence variation during the process of allopolyploidization have not been well understood. In this study, the inter-tRNA gene corresponding to tRNA amplification polymorphism method was used to detect changes in tRNA gene sequences in the progeny of interspecific hybrids between Brassica rapa and B. oleracea, mimicking the original B. napus (canola) species formation event. Cluster analysis showed that tRNA gene variation during allopolyploidization did not appear to have a genotypic basis. Significant variation occurred in the early generations of synthetic B. napus (F and F generations), but fewer alterations were observed in the later generation (F). The variation-prone tRNA genes tended to be located in AT-rich regions. BlastN analysis of novel tRNA gene variants against a Brassica genome sequence database showed that the variation of these tRNA-gene-associated sequences in allopolyploidization might result in variation of gene structure and function, e.g., metabolic process and transport

Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: a Mendelian randomization study

BackgroundResearch has shown that the disordered serum lipid profile may be associated with the risk of differentiated thyroid cancer (DTC). Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causality of circulating lipoprotein lipids on DTC.MethodsMendelian randomization (MR) analysis was conducted to evaluate the relationship between the circulating lipoprotein lipids and DTC risk using single-nucleotide polymorphisms (SNPs) from a genome-wide association (GWA) study containing a high-incidence Italian population of 690 cases samples with DTC and 497 controls.ResultsUnivariate and multivariate mendelian randomization analysis demonstrated that ‘total cholesterol’, ‘HDL cholesterol’, ‘apolipoprotein B’ and ‘ratio of apolipoprotein B to apolipoprotein A1’ were correlated with DTC. According to sensitivity analysis, our results were reliable. Furthermore, multivariate analysis revealed that there is no causative association between DTC and any of the many cause factors when they interact with one another, suggesting that there was a deep interaction between the four factors, which could affect each other. Finally, the mechanism of the related effects each other as well as the target genes with significant SNP regulatory effects in DTC was explored by conducting functional enrichment analysis and constructing the regulatory networks.ConclusionsWe obtained four exposure factors (total cholesterol, HDL cholesterol, apolipoprotein B and ratio of apolipoprotein B to apolipoprotein A1) closely related to DTC, which laid a theoretical foundation for the treatment of DTC

Unique allosteric effect driven rapid adsorption of carbon dioxide on a new ionogel [P4444][2-Op]@MCM-41 with excellent cyclic stability and loading-dependent capacity

Allosteric effect-driven rapid stepwise CO2 adsorption of pyridine-containing anion functionalized ionic liquid [P4444][2-Op] confined into mesoporous silica MCM-41.</p

GPT-4V in Wonderland: Large Multimodal Models for Zero-Shot Smartphone GUI Navigation

We present MM-Navigator, a GPT-4V-based agent for the smartphone graphical user interface (GUI) navigation task. MM-Navigator can interact with a smartphone screen as human users, and determine subsequent actions to fulfill given instructions. Our findings demonstrate that large multimodal models (LMMs), specifically GPT-4V, excel in zero-shot GUI navigation through its advanced screen interpretation, action reasoning, and precise action localization capabilities. We first benchmark MM-Navigator on our collected iOS screen dataset. According to human assessments, the system exhibited a 91\% accuracy rate in generating reasonable action descriptions and a 75\% accuracy rate in executing the correct actions for single-step instructions on iOS. Additionally, we evaluate the model on a subset of an Android screen navigation dataset, where the model outperforms previous GUI navigators in a zero-shot fashion. Our benchmark and detailed analyses aim to lay a robust groundwork for future research into the GUI navigation task. The project page is at https://github.com/zzxslp/MM-Navigator.Comment: Work in progres

Optimization of genetic distance threshold for inferring the CRF01_AE molecular network based on next-generation sequencing

IntroductionHIV molecular network based on genetic distance (GD) has been extensively utilized. However, the GD threshold for the non-B subtype differs from that of subtype B. This study aimed to optimize the GD threshold for inferring the CRF01_AE molecular network.MethodsNext-generation sequencing data of partial CRF01_AE pol sequences were obtained for 59 samples from 12 transmission pairs enrolled from a high-risk cohort during 2009 and 2014. The paired GD was calculated using the Tamura-Nei 93 model to infer a GD threshold range for HIV molecular networks.Results2,019 CRF01_AE pol sequences and information on recent HIV infection (RHI) from newly diagnosed individuals in Shenyang from 2016 to 2019 were collected to construct molecular networks to assess the ability of the inferred GD thresholds to predict recent transmission events. When HIV transmission occurs within a span of 1-4 years, the mean paired GD between the sequences of the donor and recipient within the same transmission pair were as follow: 0.008, 0.011, 0.013, and 0.023 substitutions/site. Using these four GD thresholds, it was found that 98.9%, 96.0%, 88.2%, and 40.4% of all randomly paired GD values from 12 transmission pairs were correctly identified as originating from the same transmission pairs. In the real world, as the GD threshold increased from 0.001 to 0.02 substitutions/site, the proportion of RHI within the molecular network gradually increased from 16.6% to 92.3%. Meanwhile, the proportion of links with RHI gradually decreased from 87.0% to 48.2%. The two curves intersected at a GD of 0.008 substitutions/site.DiscussionA suitable range of GD thresholds, 0.008-0.013 substitutions/site, was identified to infer the CRF01_AE molecular transmission network and identify HIV transmission events that occurred within the past three years. This finding provides valuable data for selecting an appropriate GD thresholds in constructing molecular networks for non-B subtypes

The Technology of Mould Steel for Online Pre-hardening

AbstractThis article describes a production method of mould steel pre-hardening, and focus on the advantage of this method, The technical core of method is the variable frequency and variable amplitude pulse uniform high-precision temperature control, which achieved by using strong-medium-weak water cooling, gas-water cooling and gas mist cooling composite cooling control technology. Optimizing the cooling rate path is a good method of optimizing quenched organization and structure