Latent space search based multimodal optimization with personalized edge-network biomarker for multi-purpose early disease prediction.

Considering that cancer is resulting from the comutation of several essential genes of individual patients, researchers have begun to focus on identifying personalized edge-network biomarkers (PEBs) using personalized edge-network analysis for clinical practice. However, most of existing methods ignored the optimization of PEBs when multimodal biomarkers exist in multi-purpose early disease prediction (MPEDP). To solve this problem, this study proposes a novel model (MMPDENB-RBM) that combines personalized dynamic edge-network biomarkers (PDENB) theory, multimodal optimization strategy and latent space search scheme to identify biomarkers with different configurations of PDENB modules (i.e. to effectively identify multimodal PDENBs). The application to the three largest cancer omics datasets from The Cancer Genome Atlas database (i.e. breast invasive carcinoma, lung squamous cell carcinoma and lung adenocarcinoma) showed that the MMPDENB-RBM model could more effectively predict critical cancer state compared with other advanced methods. And, our model had better convergence, diversity and multimodal property as well as effective optimization ability compared with the other state-of-art methods. Particularly, multimodal PDENBs identified were more enriched with different functional biomarkers simultaneously, such as tissue-specific synthetic lethality edge-biomarkers including cancer driver genes and disease marker genes. Importantly, as our aim, these multimodal biomarkers can perform diverse biological and biomedical significances for drug target screen, survival risk assessment and novel biomedical sight as the expected multi-purpose of personalized early disease prediction. In summary, the present study provides multimodal property of PDENBs, especially the therapeutic biomarkers with more biological significances, which can help with MPEDP of individual cancer patients.

Multi-modal optimization to identify personalized biomarkers for disease prediction of individual patients with cancer.

Finding personalized biomarkers for disease prediction of patients with cancer remains a massive challenge in precision medicine. Most methods focus on one subnetwork or module as a network biomarker; however, this ignores the early warning capabilities of other modules with different configurations of biomarkers (i.e. multi-modal personalized biomarkers). Identifying such modules would not only predict disease but also provide effective therapeutic drug target information for individual patients. To solve this problem, we developed a novel model (denoted multi-modal personalized dynamic network biomarkers (MMPDNB)) based on a multi-modal optimization mechanism and personalized dynamic network biomarker (PDNB) theory, which can provide multiple modules of personalized biomarkers and unveil their multi-modal properties. Using the genomics data of patients with breast or lung cancer from The Cancer Genome Atlas database, we validated the effectiveness of the MMPDNB model. The experimental results showed that compared with other advanced methods, MMPDNB can more effectively predict the critical state with the highest early warning signal score during cancer development. Furthermore, MMPDNB more significantly identified PDNBs containing driver and biomarker genes specific to cancer tissues. More importantly, we validated the biological significance of multi-modal PDNBs, which could provide effective drug targets of individual patients as well as markers for predicting early warning signals of the critical disease state. In conclusion, multi-modal optimization is an effective method to identify PDNBs and offers a new perspective for understanding tumor heterogeneity in cancer precision medicine.

The effect of KH on enhancing the dehydrogenation properties of the Li-N-H system and its catalytic mechanism.

Although recent works demonstrated that some potassium compounds that can be converted to KH during ball-milling or heat-treatment have obvious effects on enhancing the dehydrogenation properties of the Li-N-H system, the effect of KH on enhancing the dehydrogenation properties of the Li-N-H system and its catalytic mechanism remain unclear. In this study, the hydrogen desorption properties of the LiNH2-LiH system with alkali metal hydrides (LiH, NaH, or KH) were investigated and discussed. We find that the three types of hydrides are effective for enhancing the hydrogen desorption properties of the LiNH2-LiH system, among which, KH shows the best effect. In comparison with the broad shaped hydrogen desorption curve of the LiNH2-LiH composite without additive, the hydrogen desorption curve of the LiNH2-LiH-0.05KH composite becomes narrow. The dehydrogenation onset temperature of the LiNH2-LiH-0.05KH composite is decreased by approximately 20 °C, and the dehydrogenation peak temperature is lowered by approximately 30 °C. Moreover, the reversibility of the LiNH2-LiH system is enhanced drastically by the addition of KH. On the basis of previous reports and present experimental results, the mechanism for the enhancement of the dehydrogenation properties in the KH-added Li-N-H system is proposed. The reason for the improvement of the hydrogen desorption kinetics is that KH has superior reactivity with NH3 and plays the role of a catalyst to accelerate hydrogen release by cyclic reactions.

Network Control Models With Personalized Genomics Data for Understanding Tumor Heterogeneity in Cancer.

Due to rapid development of high-throughput sequencing and biotechnology, it has brought new opportunities and challenges in developing efficient computational methods for exploring personalized genomics data of cancer patients. Because of the high-dimension and small sample size characteristics of these personalized genomics data, it is difficult for excavating effective information by using traditional statistical methods. In the past few years, network control methods have been proposed to solve networked system with high-dimension and small sample size. Researchers have made progress in the design and optimization of network control principles. However, there are few studies comprehensively surveying network control methods to analyze the biomolecular network data of individual patients. To address this problem, here we comprehensively surveyed complex network control methods on personalized omics data for understanding tumor heterogeneity in precision medicine of individual patients with cancer.

The facilitating role of dispositional mindfulness in the process of posttraumatic growth: A prospective investigation.

OBJECTIVE: Traumatic events can lead not only to psychological distress but also to posttraumatic growth (PTG). As trauma challenge one's fundamental assumptions, traumatized individuals may initially experience intrusive rumination. However, these challenged assumptions could facilitate further cognitive processing of trauma (i.e., deliberate rumination), which in turn fosters PTG. Adaptive cognitive processes, such as reduced rumination, have been linked to dispositional mindfulness. Thus, the current study aimed to investigate the potential role of dispositional mindfulness in the process of PTG. METHOD: A 3-wave longitudinal design was employed to capture temporal changes in PTG. At the initial assessment (time 1), 259 traumatized individuals were assessed with regard to their trauma experiences, core belief challenge, intrusive and deliberate rumination, posttraumatic stress symptoms (PTSS), PTG, and dispositional mindfulness. The surveys were repeated after 1 month (time 2) and 7 months (time 3). RESULTS: Over time, the first indirect association of core belief challenge was increased PTG through recent intrusive and deliberate rumination, and the second indirect association of core belief challenge was decreased PTG through recent intrusive rumination and PTSS. In addition, dispositional mindfulness significantly moderated these 2 indirect associations. Individuals with a medium level of mindfulness at time 1 had lower levels of rumination and PTSS at time 3 compared to individuals with a low level of mindfulness. CONCLUSIONS: In the face of trauma, dispositional mindfulness promotes resilience through a subsequent reduction in rumination and PTSS. Our results highlight the protective role of dispositional mindfulness in long-term outcomes of trauma exposure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Atomically dispersed Fe-N-C catalyst displaying ultra-high stability and recyclability for efficient electroreduction of CO2 to CO.

To avoid the agglomeration of iron NPs and improve the dispersion of Fe SAs, we employed a mixed-ligand strategy to regulate the iron content in PCN-224(ZnxFey) and PCN-222(ZnxFey). Thanks to the sublimation of Zn and the Kirkendall effect, uniform dispersions of Fe SAs with 1.04-1.06 wt% were obtained in the pyrolysis products Zn0.5Fe0.5-N-C-224 and Zn0.5Fe0.5-N-C-222 with excellent CO2 → CO activity, super-stability, and recyclability.

[MG-132 enhances MSCs survival and IL-10 secretion under hypoxia and serum deprivation condition].

Bone marrow-derived mesenchymal stem cells (MSCs) have emerged as attractive candidates for cellular therapies for heart and other organ-system disorders. However, a major dilemma in stem cell therapy for ischemic heart diseases is the low survival of transplanted cells in the ischemic and peri-infarcted region. In this study, MSCs were treated by hypoxia and serum deprivation (H/SD) to mimic the ischemic microenvironment of infarcted hearts where MSCs were transplanted. The effects of proteasome inhibitor MG-132 on H/SD-induced apoptosis and paracrine effects were investigated. Apoptosis of MSCs was detected by Annexin V-FITC flow cytometric analysis. Transcriptional levels of IL-1ß, TNF-α and IL-10 were examined by real-time PCR. The nuclear translocation of NF-κBp65 was assessed by immunocytochemical staining. Translational changes of IL-1ß and TNF-α were detected by Western blot. The secretion of IL-10 from MSCs was examined by ELISA assay. The results showed that MG-132 could effectively suppress H/SD-induced MSCs apoptosis. Furthermore, the induced IL-1ß and TNF-α transcription was also inhibited by MG-132 treatment, which may be due to the inhibition of NF-κBp65 nuclear translocation by MG-132. Importantly, MG-132 effectively enhanced H/SD-induced transcription and secretion of IL-10, which is an important paracrine factor from MSCs. Our findings suggest that pretreatment of MSCs by MG-132 before cell transplantation may be an effective strategy to improve cell survival and enhance paracrine effects of MSCs.

[Function and biological activities of the autotaxin-LPA axis].

Autotaxin (ATX), a member of nucleotide pyrophosphatase/phosphodiesterase (NPP) family, is also named as phosphodiesterase Iα (PD-Iα) or NPP2. ATX is the unique member among the NPPs that can function as a lysophospholipase D (lysoPLD), converting lysophosphatidylcholine into lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors to elicit a wide range of cellular response, including cell proliferation, cell migration and cell contraction, etc. As the major LPA-producing phospholipase, many ATX's features and functions are dependent on the production of LPA. ATX and LPA together form the ATX-LPA functional axis. The present review summarizes the current progress in function and biological activities of ATX-LPA axis.

[Pharmacokinetics and bioavailability of sustained-release tablets of matrine in dogs].

OBJECTIVE: To study the pharmacokinetics and bioavailability of sustained-release tablets of Matrine in dogs. METHODS: 6 dogs were randomly assigned to receive sustained-release tablets or commercial capsules 300 mg, then a crossover trial was conducted 1 week later. Plasma samples were taken at different time points and the plasma concentration of Oxymatrine and Matrine in dogs was determined by HPLC. RESULTS: The pharmacokinetic parameters of self-made sustained-release tablets versus those of its control preparation were as follows: Tmax: (6.17 +/- 2.04) (M), (3.25 +/- 0.61) (OM), (4.75 +/- 1.17) (M), (2.42 +/- 0.38) (OM) h; Cmax: (3.79 +/- 1.11) (M), (4.76 +/- 0.60) (OM), (5.35 +/- 0.72) (M), (7.04 +/- 0.47) (OM) microg/mL; AUC(0-->infinity): (45.15 +/- 11.77) (M), (32.38 +/- 4.60) (OM) and (44.71 +/- 5.52) (M), (29.11 +/- 4.41) (OM) microg x h/mL. CONCLUSION: The self-made sustained-release tablets and commercial capsules bioequivalent.

Revealing the structure-activity relationship of two Cu-porphyrin-based metal-organic frameworks for the electrochemical CO2-to-HCOOH transformation.

The eCO2RR activity is correlated to the internal structural character of the catalyst. We employed two types of structural models of porphyrin-based MOFs of PCN-222(Cu) and PCN-224(Cu) into heterogeneous catalysis to illustrate the effect of structural factors on the eCO2RR performance. The composite catalyst PCN-222(Cu)/C displays better activity and selectivity (η = 450 mV, FEHCOOH = 44.3%, j = 3.2 mA cm-2) than PCN-224(Cu)/C (η = 450 mV, FEHCOOH = 34.1%, j = 2.4 mA cm-2) for the CO2 reduction to HCOOH in the range of -0.7--0.9 V (vs. RHE) due to its higher BET surface area, CO2 uptake, and a larger pore diameter. It is interesting that PCN-224(Cu)/C displays better performance in the range of -0.4--0.6 V (vs. RHE) due to its greater heat of adsorption, Qst and a higher affinity for CO2 molecule, which could promote the capture of CO2 onto the exposed active sites. As a result, PCN-224(Cu)/C exhibits better stability for the long-term electrolysis.

P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis.

INTRODUCTION: Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. AIM: To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. RESULTS: The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1ß, IL-6, IL-10, TNF-α, TGF-ß, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis. CONCLUSION: Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.

[The study of fermentation liquid's absorption spectra in elastase fermentation].

The present article studied the fermentation liquid's absorption spectra, bacteria growth period and elastase' production in elastase fermentation, and compared and analyzed the their relation. The results show that the changes in the absorption spectra were closely related with bacteria growth and elastase' production. The UV spectroscopic technique is helpful for detecting the change of the organic nitrogen base and enzyme. The study offers a new method to detect fermentation process and is basic for detecting fermentation process on line by UV spectroscopic technique.

Construction of (3,6)-connected polyoxometalate-based metal-organic frameworks (POMOFs) from triangular carboxylate and dimerized Zn4-ε-Keggin.

Using the methodology of extension of reduced transition metal-grafted ε-Keggin polyoxoanions with two types of terphenyl-based tricarboxylates of H3L1 (3,5',3''-position substitution) and H3L2 (4,5',4''-position substitution) we isolated two (3,6)-connected 3D polyoxometalate-based metal-organic frameworks, [TBA]3[H3PMo12O40][Zn4L2] (1, YZU-105), and [TPA]3[H3PMo12O40][Zn4L1]·0.5H2O (2, YZU-106) (H3L1 = [1,1';3',1''-terphenyl]-3,5',3''-tricarboxylic acid; H3L2 = [1,1';3',1''-terphenyl]-4,5',4''-tricarboxylic acid; TBA = tetrabutylammonium; TPA = tetrapropylammonium). In both compounds, the building block was the dimerized form of Zn4-{ε-H3PMo12O40}. Such dimerization left six anchoring points for each dimer and, as a result, a 6-connected node was formed. Compounds 1 and 2 exhibited topologies of (4·85)3(4·82)6 and (65·10)3(63)6, respectively. This work illustrates that use of tri-carboxylate substitutions in different positions (3,5',3''-position/4,5',4''-position) in tripodal terphenyl-based ligands allows different extents of twisting of the peripheral aromatic ring with respect to the central ring, thereby giving rise to different extending directions and symmetries.

[Study on ion beam mutagenizing of the Trichosporon lactis T for enantioselective separation of ibuprofen].

The initial strain, Trichosporon Lactis T, isolated from soil sample, having the capability of enantioselectively hydrolyzing S-isomer of racemic ibuprofen ethyl-ester into the corresponding S-ibuprofen, was implanted by 30 KeV, 1 x 10(15) ions/cm2 - 5 x 10(15) ions/cm2 low-energy N+ for the purpose of obtaining mutants with high-efficiency hydrolyzing enzyme to produce active S-ibuprofen. Under the dosage of 30 KeV, 4 x 10(15) ions/cm2, the mutation rate is the highest, with 32.9 % positive and 37.1% negative mutant, respectively. Therefore, 30 KeV, 4 x 10(15) ions/cm2 is chosen as the optimal implantation dosage. Under optimal implantation dosage, seven mutants with high-efficiency hydrolyzing enzyme are selected after N+ implantation. The genetic stability test shows that T. lactis K1, one of the seven mutants, has a stable hydrolyzing ability during consecutive five-generation. The enzyme activity of T. lactis K1 is higher with 50% than that of the initial strain after 24 h cultivation, and the highest enzyme activity of T. lactis K1 appears 6h earlier than that of the initial strain. After 24 h cultivation and succeeding 24 h incubation with ibuprofen ethyl ester, the S-ibuprofen production of T. lactis K1 is 6.96 g/L, 64.2% higher than that of T. lactis T, which only produces 4.24 g/L S-ibuprofen at the same time, the specific rotation and enantiomeric excess (ee%) of the S-ibuprofen produced by two stains, however, are the same, + 54.1 degrees and 98%, respectively.

GRP78 secreted by colon cancer cells facilitates cell proliferation via PI3K/Akt signaling.

Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/ß-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.