MKG-GC: A multi-task learning-based knowledge graph construction framework with personalized application to gastric cancer.

Over the past decade, information for precision disease medicine has accumulated in the form of textual data. To effectively utilize this expanding medical text, we proposed a multi-task learning-based framework based on hard parameter sharing for knowledge graph construction (MKG), and then used it to automatically extract gastric cancer (GC)-related biomedical knowledge from the literature and identify GC drug candidates. In MKG, we designed three separate modules, MT-BGIPN, MT-SGTF and MT-ScBERT, for entity recognition, entity normalization, and relation classification, respectively. To address the challenges posed by the long and irregular naming of medical entities, the MT-BGIPN utilized bidirectional gated recurrent unit and interactive pointer network techniques, significantly improving entity recognition accuracy to an average F1 value of 84.5% across datasets. In MT-SGTF, we employed the term frequency-inverse document frequency and the gated attention unit. These combine both semantic and characteristic features of entities, resulting in an average Hits@ 1 score of 94.5% across five datasets. The MT-ScBERT integrated cross-text, entity, and context features, yielding an average F1 value of 86.9% across 11 relation classification datasets. Based on the MKG, we then developed a specific knowledge graph for GC (MKG-GC), which encompasses a total of 9129 entities and 88,482 triplets. Lastly, the MKG-GC was used to predict potential GC drugs using a pre-trained language model called BioKGE-BERT and a drug-disease discriminant model based on CNN-BiLSTM. Remarkably, nine out of the top ten predicted drugs have been previously reported as effective for gastric cancer treatment. Finally, an online platform was created for exploration and visualization of MKG-GC at https://www.yanglab-mi.org.cn/MKG-GC/.

A gene signature linked to fibroblast differentiation for prognostic prediction of mesothelioma.

BACKGROUND: Malignant mesothelioma is a type of infrequent tumor that is substantially related to asbestos exposure and has a terrible prognosis. We tried to produce a fibroblast differentiation-related gene set for creating a novel classification and prognostic prediction model of MESO. METHOD: Three databases, including NCBI-GEO, TCGA, and MET-500, separately provide single-cell RNA sequencing data, bulk RNA sequencing profiles of MESO, and RNA sequencing information on bone metastatic tumors. Dimensionality reduction and clustering analysis were leveraged to acquire fibroblast subtypes in the MESO microenvironment. The fibroblast differentiation-related genes (FDGs), which were associated with survival and subsequently utilized to generate the MESO categorization and prognostic prediction model, were selected in combination with pseudotime analysis and survival information from the TCGA database. Then, regulatory network was constructed for each MESO subtype, and candidate inhibitors were predicted. Clinical specimens were collected for further validation. RESULT: A total of six fibroblast subtypes, three differentiation states, and 39 FDGs were identified. Based on the expression level of FDGs, three MESO subtypes were distinguished in the fibroblast differentiation-based classification (FDBC). In the multivariate prognostic prediction model, the risk score that was dependent on the expression level of several important FDGs, was verified to be an independently effective prognostic factor and worked well in internal cohorts. Finally, we predicted 24 potential drugs for the treatment of MESO. Moreover, immunohistochemical staining and statistical analysis provided further validation. CONCLUSION: Fibroblast differentiation-related genes (FDGs), especially those in low-differentiation states, might participate in the proliferation and invasion of MESO. Hopefully, the raised clinical subtyping of MESO would provide references for clinical practitioners.

[Effect of catgut implantation on macrophage CD68, tumor necrosis factor-α and interleukin-1ß in "Zusanli" (ST 36) region of rats].

OBJECTIVE: To observe the expression of local macrophages and related cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) after catgut implantation in "Zusanli"(ST 36) in rats, so as to explore its underlying mechanisms in inducing therapeutic effect. METHODS: A total of 110 male SD rats were randomly divided into blank control group (n=10), catgut embedding (CE) group (n=50), and sham CE group (n=50). The CE and sham CE groups were randomly divided into 8 h, 3 d, 7 d, 14 d and 21 d subgroups after the intervention (n=10 in each time point group). Rats of the CE group were uniformly subjected into catgut embedding at ST36 once, and those of the sham CE group received embedding needle puncture at ST36 without catgut retention, and the blank control group was only grasped and fixed without other treatments. Tissues from the ST36 area in each group were collected at the corresponding time points, and the expression of CD68 in macrophages in the acupoint area was detected by immunofluorescence, the contents of TNF-α and IL-1ß in the acupoint area were detected by ELISA. RESULTS: Following catgut embedment at ST36, the contents of TNF-α and IL-1ß, and macrophage CD68 expression level began to increase at 8 h, peaked at 3 d, and then gradually decreased at 7, 14, and 21 d, being still higher in the CE group than in the blank control group at 21 d (P<0.05). Compared with the blank control group, the contents of TNF-α and IL-1ß, and macrophage CD68 expression were significantly increased at 8 h, and 3, 7, 14 and 21 d in the CE group (P<0.05). Following sham CE at ST36, the content of TNF-α at 8 h and 3 d, IL-1ß at 8 h and 3, 7 and 14 d, and expression of CD68 at 8 h were significantly increased in comparison with the blank control group (P<0.05). Comparison between the CE and sham CE groups showed that the contents of IL-1ß at 3, 7, 14 and 21 d, and contents of TNF-α，CD68 expression at 8 h, and 3, 7, 14 and 21 d were significantly higher in the CE group than in the sham CE group (P<0.05). CONCLUSION: Catgut embedding at ST36 can induce an increase levels of inflammatory cytokines TNF-α, IL-1ß and macrophage CD68 in the local microenvironment in rats, which may contribute to its functions in initiating therapeutic effect.

Heavy metals immobilization of ternary geopolymer based on nickel slag, lithium slag and metakaolin.

To solve heavy metals leaching problem in the utilization of various industrial solid wastes, this work investigated the heavy metals immobilization of ternary geopolymer prepared by nickel slag (NS), lithium slag (LS), and metakaolin (MK). Compressive strength was measured to determine the optimum and appropriate mix proportions. The leaching characteristics of typical heavy metals (Cu (Ⅱ), Pb (Ⅱ), and Cr (Ⅲ)) in acid, alkali, and salt environments were revealed by Inductively Coupled Plasma (ICP). The heavy metals immobilization mechanism was explored by Mercury Intrusion Porosimetry (MIP), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) tests. The experimental results show that the group with a mass ratio of NS, LS and MK of 1:1:8 exhibits the highest compressive strength, which reaches 69.1 MPa at 28 d. The ternary geopolymer possesses a desirable capacity for immobilizing inherent heavy metals, where the immobilization rates of Cu and Pb reach 96.69 %, and that of Cr reaches 99.97 %. The leaching concentrations of Cr and Pb increase when the samples are exposed to acidic and alkaline environments. Cu and Pb are mainly physically encapsulated in geopolymer. Additionally, immobilization of Cr mainly involves physical encapsulation and chemical bonding.

Pan-cancer analysis reveals signal transducer and activator of transcription (STAT) gene family as biomarkers for prognostic prediction and therapeutic guidance.

Background: The signal transducer and activator of transcription (STAT) gene family have been widely found to regulate cell proliferation, differentiation, apoptosis, and angiogenesis through complex signaling pathways, and thus impacting tumor formation and development in different types of tumor. However, the roles of STATs on prognostic prediction and therapeutic guidance in pan-cancer remain unexplored. Materials and Methods: The dataset of 33 types of TCGA tumor, para-carcinoma and normal tissues, was obtained from the UCSC Xena database, including the gene expression profiles in the formats of FPKM value, demographic characteristics, clinical information, and survival data of STATs. Differential expression and co-expression analyses, WGCNA, clinical relevance analysis, immune subtype analysis, tumor stemness analysis, tumor purity analysis, immune infiltration analysis, immunotherapy related analysis, tumor mutation related analysis, and drug sensitivity analysis were performed by R software. Results: Differential expression of STAT1 was found between normal and BRCA tissues (p < 0.001, log2FC = 0.895). Additionally, the strongest correlation among STATs lied between STAT1 and STAT2 (correlation coefficient = 0.6). Moreover, high expression levels of STAT1 (p = 0.031) were revealed to be notably correlated with poor prognosis in KIRP. In addition, STAT1 expressed the highest value in immune subtypes C1, C2, C3, and C6 in LUAD. What's more, strong negative correlations were demonstrated between expression of STAT6 and mDNAss and mRNAss of TGCT. Additionally, STAT4 expression was characterized to be significantly negatively correlated with tumor purity of the majority of cancer types. Moreover, STAT1 and STAT3 were shown to be generally high-expressed in pan-cancer myeloid cells, and STATs all had positive correlation with the infiltration of the majority of immune cells. In addition, STATs were revealed to be closely linked with immunotherapy response. What's more, STAT4 expression was identified to have a strong negative correlation with TMB value in DLBC. Last but not least, positive correlations were accessed between STAT5 and sensitivity of Nelarabine (cor = 0.600, p < 0.001). Conclusion: In the present study, we identified STATs as biomarkers for prognostic prediction and therapeutic guidance in pan-cancer. Hopefully our findings could provide a valuable reference for future STATs research and clinical applications.

[Effect of moxibustion combined with acupoint catgut embedding on IL-6/JAK/STAT3 signaling pathway in colonic mucosa of ulcerative colitis rats].

OBJECTIVE: To observe the effect of moxibustion combined with acupoint catgut embedding on the content of interleukin 6 (IL-6), and the expressions of janus activated kinase (JAK), signal transducer and activator of transcription 3 (STAT3) in colonic mucosa of rats with ulcerative colitis (UC), so as to explore its mechanism underlying improvement of UC. METHODS: Thirty SD rats were randomly divided into normal, model, acupoint catgut embedding (ACE), moxibustion and acupoint catgut embedding combined with moxibustion (combination) groups (n=6 rats in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral "Tianshu" (ST25), "Dachangshu" (BL25) and "Shangjuxu" (ST37) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed by H.E. staining, the level of IL-6 in colonic mucosa was assayed by ELISA, and the expressions of JAK and STAT3 in colonic mucosa were detected by immunohistochemistry and Western blot. RESULTS: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and combination groups. After modeling, the content of colonic IL-6, and the expression levels of JAK and STAT3 were obviously increased (P<0.01) in the model group relevant to the normal group. Following the intervention, the increase of IL-6 contents, and JAK and STAT3 expressions were reversed (P<0.05, P<0.01) in moxibustion, ACE and combination groups. The therapeutic effects of moxibustion combined with ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of JAK and STAT3 expression (P<0.01). CONCLUSION: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effect in suppressing the activation of IL-6/JAK/STAT3 signaling pathway.

Theoretical Prediction on the New Types of Noble Gas Containing Anions OBONgO- and OCNNgO- (Ng = He, Ar, Kr and Xe).

The fluorine-less noble gas containing anions OBONgO- and OCNNgO- have been studied by correlated electronic structure calculation and density functional theory. The obtained energetics indicates that for Ng = Kr and Xe, these anions should be kinetically stable at low temperature. The molecular structures and electron density distribution suggests that these anions are stabilized by ion-induced dipole interactions with charges concentrated on the electronegative OBO and OCN groups. The current study shows that in addition to the fluoride ion, polyatomic groups with strong electronic affinities can also form stable noble gas containing anions of the type Y-…NgO.

Simultaneous detection of transcribed functional assA gene and the corresponding metabolites of linear alkanes (C4, C5, and C7) in production water of a low-temperature oil reservoir.

Methanogenic hydrocarbon degradation is an important biogeochemical process in oil reservoirs; however, genomic DNA-based analysis of microorganisms and metabolite detection are not conclusive for identification of the ongoing nature of this bioprocess. In this study, a suite of analyses, involving the study of microbial community and selective gene quantification of both genomic DNA and RNA together with signature metabolites, were performed to comprehensively advance the understanding of the methanogenic biodegradation of hydrocarbons in a low-temperature oilfield. The fumarate addition products for alkanes-C4, C5, and C7-alkylsuccinates-and transcribed assA and mcrA genes were simultaneously detected in the production water sample, providing robust and convincing evidence for both the initial activation of n-alkanes and methane metabolism in this oilfield. The clone library of assA gene transcripts showed that Smithella was active and most likely responsible for the addition of fumarate to n-alkanes, whereas Methanoculleus and Methanothrix were the dominant and active methane-producers via CO2 reduction and acetoclastic pathways, respectively. Additionally, qPCR results of assA and mcrA genes and their transcribed gene copy numbers revealed a roughly similar transcriptional activity in both n-alkanes-degraders and methane producers, implying that they were the major participants in the methanogenic degradation of n-alkanes in this oilfield. To the best of our knowledge, this is the first report presenting sufficient speculation, through detection of signature intermediates, corresponding gene quantification at transcriptional levels, and microbial community analysis, of methanogenic degradation of n-alkanes in production water of an oil reservoir.

[Time-effect reaction observation of micro-invasion embedded poly glycolide-co-lactide suture in Sanyinjiao (SP6) in healthy subjects by using magnetic resonance].

OBJECTIVE: To observe the time-effect of stimulation of the embedded poly glycolide-co-lactide (PGLA) suture in Sanyinjiao (SP6) area in normal human body, so as to provide an experimental evidence for clinical application of micro-invasion suture-embedding at an appropriate interval. METHODS: A total of 8 healthy volunteer students (3 boys and 5 girls, ranging in age from 24 to 27 years) were recruited in the present study. A piece of sterilized PGLA suture was implanted into the left SP6 using minimally invasive surgery after strict local skin disinfection. The fat-suppression T2 weighted magnetic resonance images (MRI, displaying local lesion after eliminating interference of fat tissue signals), and T2 mapping 8-echo train images were acquired before and 8 h, 3, 7, 10 and 14 days after PGLA suture embedment by using a MR imaging system. After transformation of the T2-mapping 8-echo train images into T2-mapping images by using a relevant software, the T2 values (meaning the relaxation time of the local muscle) of the left SP6 were measured, followed by analysis of the signal intensity of T2 weighted fat-suppression images and T2 values at different time-points. RESULTS: Before the suture embedding, no abnormal signals were found in the signal intensity of T2 weighted fat-suppression images. After PGLA suture embedment, the local signal intensity of T2WI fat-suppression images was relatively increased at the 8th h, and on day 3, 7, 10 and 14 relevant to pre-embedment, but gradually atte-nuated on day 10 and 14. The T2 values were significantly increased at the 5 time-points of post-embedment (all P<0.01), but without significant differences among the 8thh, the 3rd and 7thd (P>0.05), and being markedly lowered on day 14 relevant to day 7 (P<0.01) in spite of being still markedly higher than that of pre-embedding (P<0.01). CONCLUSION: The signal intensity of T2 weighted fat-suppression images and T2 values acquired from PGLA-suture-embedded SP6 acupoint area in healthy subjects may keep at least for 2 weeks, suggesting that the stimulating reaction of suture-embedment persists more than 14 days. Hence, when a micro-invasion embedding with PGLA suture performed, the interval of two weeks would be appropriate.

Association study between the TP53 Rs1042522G/C polymorphism and susceptibility to systemic lupus erythematosus in a Chinese Han population.

Tumour suppressor protein 53 (p53) plays a central role in apoptosis, cell proliferation and death. Previously studies found contribution of functional p53 Arg72Pro polymorphism (TP53 rs1042522G/C polymorphism) in the development of systemic lupus erythematosus (SLE) remains controversial. In this study, for the first time, we evaluated its association with SLE in a Chinese Han population. This case-control study enrolled 1470 SLE patients and 2283 healthy controls. The genotyping of TP53 rs1042522 polymorphism was determined by Sequenom Mass ARRAY technology. Statistical analysis was conducted by Chi-square test (χ 2 test). Odds ratio (OR) with 95% confidence interval (CI) was calculated using unconditional logistic regression with adjusting age and sex. Allele and genotype frequencies of TP53 rs1042522G/C polymorphism showed statistically significant difference between the SLE patients and the normal controls (C vs. G: OR = 0.89, 95% CI 0.89-0.97, p = 0.01; (GC + CC) vs. GG using recessive model: OR = 0.84, 95% CI 0.73-0.96, p = 0.01; GC vs. GG using co-dominant model: OR = 0.86, 95% CI 0.74-0.99, p = 0.04; CC vs. GG using co-dominant model: OR = 0.80, 95% CI 0.66-0.96, p = 0.02; GC vs. GG using co-dominant model: OR = 0.86, 95% CI 0.74-0.99, p = 0.02). In addition, there was weak association between discoid rash and distribution of TP53 rs1042522G/C polymorphism in SLE patients (C vs. G: OR = 1.25, 95% CI 1.00-1.55, p = 0.04; CC vs. GG using co-dominant model: OR = 1.54, 95% CI 1.10-2.36, p = 0.04). Our finding suggests a significant relationship between the TP53 rs1042522G/C polymorphism and SLE. TP53 rs1042522G/C polymorphism would be promising as an indicator of SLE as well as the therapeutic target if its functions and mechanisms could be further investigated.