It is widely accepted that the incorporation of external sulfur via crustal contamination is an important trigger for sulfide immiscibility that generates Ni-Cu-(PGE) sulfide mineralization, yet ...other controlling factors for sulfide immiscibility may also be present. The late Permian Panzhihua, Baima, Hongge, Xinjie and Taihe layered intrusions in the Emeishan Large Igneous Province (ELIP, SW China), are well-endowed with Fe-Ti oxide deposits, whereas their sulfide mineralization is mainly sub-economic. For example, the lower part of the Xinjie intrusion hosts a few thin PGE-rich ore layers, yet other ELIP layered intrusions do not contain any Ni-Cu sulfide mineralization and are PGE-depleted (0.01-1 ppb). Compared with the PGE-undepleted Emeishan high-Ti basalts that are genetically related to the intrusions, the extent of PGE depletion and elevated Cu/Pd ratios (up to 3.2x10^sup 6^) of the Panzhihua, Baima, Taihe and Hongge intrusions suggest PGE-depletion in their parental magmas due to early-stage sulfide removal. Sr-Nd isotopic compositions of the Panzhihua, Baima and Taihe intrusions suggest crustal contamination was insignificant and sulfide saturation produced mainly by crustal sulfur input was unlikely. MELTS modeling shows that extensive fractionation of chromite, olivine and clinopyroxene in deep-seated magma chambers may have induced early-stage sulfide saturation of the primary magmas. The relatively high sulfide contents in the Fe-Ti oxide layers at Panzhihua, Baima, Hongge and Taihe indicate a close relationship between the second-stage sulfide immiscibility and extensive Fe-Ti oxide crystallization. Positive correlations between sulfur and total Fe^sub 2^O^sub 3^, V and TiO^sub 2^ suggest that Fe-Ti oxide (magnetite and ilmenite) crystallization may have triggered the second-stage sulfide saturation via sharply lowering the Fe concentration and oxygen fugacity of the magmas. Moderate degree of crustal contamination for the Xinjie Fe-Ti oxide-barren rocks may have induced sulfide saturation and accumulation at the lower part of the intrusion. Our calculations indicate that the Xinjie PGE-rich rocks have high R-factors (1000-10000), which are ascribed to PGE-upgrading of the sulfides via reaction with new replenishments of PGE-undepleted magmas. A few Panzhihua, Baima and Taihe samples that contain higher PGE concentrations suggest that the early-stage sulfide droplets at depths were entrained in later magma pulses delivered to shallower magma chambers. The very high R-factors determined by mass balance calculation, implies a good potential for discovering more PGE mineralization in the deep-seated intrusions of the magma plumbing system.
To date, there are no effective treatments for most neurodegenerative diseases. Knowledge graphs can provide comprehensive and semantic representation for heterogeneous data, and have been ...successfully leveraged in many biomedical applications including drug repurposing. Our objective is to construct a knowledge graph from literature to study relations between Alzheimer's disease (AD) and chemicals, drugs and dietary supplements in order to identify opportunities to prevent or delay neurodegenerative progression. We collected biomedical annotations and extracted their relations using SemRep via SemMedDB. We used both a BERT-based classifier and rule-based methods during data preprocessing to exclude noise while preserving most AD-related semantic triples. The 1,672,110 filtered triples were used to train with knowledge graph completion algorithms (i.e., TransE, DistMult, and ComplEx) to predict candidates that might be helpful for AD treatment or prevention. Among three knowledge graph completion models, TransE outperformed the other two (MR = 13.45, Hits@1 = 0.306). We leveraged the time-slicing technique to further evaluate the prediction results. We found supporting evidence for most highly ranked candidates predicted by our model which indicates that our approach can inform reliable new knowledge. This paper shows that our graph mining model can predict reliable new relationships between AD and other entities (i.e., dietary supplements, chemicals, and drugs). The knowledge graph constructed can facilitate data-driven knowledge discoveries and the generation of novel hypotheses.
AIM: To explore the application feasibility of problem-based learning(PBL)teaching mode in ophthalmology class in medical colleges of China.METHODS: Totally 157 students of class 2009 in Yangtze ...University majoring in clinical medicine were surveyed by questionnaires.RESULTS: The survey showed that 77.9% of students thought that traditional teaching methods of ophthalmology classes were quite satisfying. 82.8% of them considered it necessary to introduce the new teaching mode. 83.4% of them would choose PBL teaching mode between the traditional teaching mode and PBL teaching mode. 56.6% of them thought that PBL teaching mode was conducive to students' self-learning ability. The subjective and objective conditions made the exploration of PBL teaching modes feasible. However, there were disadvantages of PBL teaching mode. 73.1% of students thought the school teaching facilities were not enough, 78.6% of students thought that only part of the content of ophthalmology teaching was suitable for using PBL teaching mode.CONCLUSION: PBL teaching mode should be continuously explored and studied in the future ophthalmology teaching, in order to create suitable for China's national conditions of ophthalmology teaching mode.
•Aidi injection can significantly increase clinical response and reduce radiochemotherapy related toxicity.•Can Aidi injection improve the survival in non-small-cell lung cancer (NSCLC)?•A ...meta-analysis was conducted of 25 RCTs involving 2662 patients with NSCLC.•Results indicated that Aidi injection can significantly improve clinical response and OS rates in patients with NSCLC and especially, the 1- and 2-year OS rate.•Aidi injection plus different therapies may have different effects on overall survival, and these need to be confirmed by new best evidences.
Aidi injection can significantly improve clinical response and reduce radiochemotherapy related toxicity. Can Aidi injection improve the survival in non-small-cell lung cancer (NSCLC)? Therefore, to further reveal it, we systematically evaluated all related studies.
We collected all studies about Aidi injection for NSCLC in Medline, Embase, Web of Science(ISI), China National Knowledge Infrastructure Database(CNKI), Chinese Scientific Journals Full-Text Database(VIP), Wanfang, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR) and WHO International Clinical Trials Registry Platform (WHO-ICTRP), and US-clinical trials (established to June 2016). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the PICO principles, and synthesized the data by meta-analysis.
We included 25 RCTs involving 2662 patients with NSCLC which most studies had unclear risk of bias. The merged risk ratios (RR) values and their 95% CI of meta-analysis for objective response rate (ORR) and disease control rate (DCR) were as following: 1.19(1.09–1.29) and 1.07(1.03–1.11). The merged RR values and their 95% CI of meta-analysis for the 1-, 2- and 3-year overall survival (OS) rate were as following: 1.23(1.14–1.33), 1.46(1.22–1.74) and 1.67(1.04–2.69). All differences were statistically significant. Subgroup analysis showed that Aidi injection plus different therapies had different effects on 1-, 2- and 3-year OS rate. Sensitivity analysis showed that the RR of ORR, DCR, 1- and 2- year OS rate had good stability, and 3-year OS rate had poor stability.
Available evidences indicate that Aidi injection can significantly improve the clinical response and OS rates in patients with NSCLC and especially, the 1- and 2-year OS rate. But, Aidi injection plus different therapies had different effects on overall survival. It is still unclear whether Aidi injection can improve the PFS and HR.
To discriminate between fentanyl derivatives with high and low activities.
The support vector classification (SVC) method, a novel approach, was employed to investigate structure-activity ...relationship (SAR) of fentanyl derivatives based on the molecular descriptors, which were quantum parameters including DeltaE energy difference between highest occupied molecular orbital energy (HOMO) and lowest empty molecular orbital energy (LUMO), MR (molecular refractivity) and M(r) (molecular weight).
By using leave-one-out cross-validation test, the accuracies of prediction for activities of fentanyl derivatives in SVC, principal component analysis (PCA), artificial neural network (ANN) and K-nearest neighbor (KNN) models were 93%, 86%, 57%, and 71%, respectively. The results indicated that the performance of the SVC model was better than those of PCA, ANN, and KNN models for this data.
SVC can be used to investigate SAR of fentanyl derivatives and could be a promising tool in the field of SAR research.
Patients with cancer have a higher incidence of cardiovascular diseases (CVDs). We aimed to evaluate the relationship between serum human epididymal protein 4 (HE4) levels and cardiovascular events ...in obese patients with breast cancer.
Serum HE4 levels in 316 obese patients with breast cancer were measured at baseline and then prospectively followed up for approximately 36 months. The prognostic value of serum HE4 for predicting cardiovascular events was analyzed by the Cox proportional hazard model.
Serum HE4 was significantly associated with CVD history after adjustment for confounding factors (OR= 1.50; 95% CI 1.23-3.43;
0.038) using multivariable logistic regression analysis. The multivariable Cox proportional hazard analysis suggested that serum HE4 had an independent prognostic value for predicting cardiovascular events in patients with breast cancer (HR=2.21, 95% CI 1.60-5.13,
<0.001). Additionally, sensitivity analysis showed that the independent association still existed. Stratified analysis showed that this relationship was not affected by chemoradiotherapy.
Serum HE4 is significantly related to cardiovascular events and poses good prognostic value for predicting cardiovascular events in obese patients with breast cancer. Serum HE4 may be a valuable indicator for the early detection of cardiovascular complications in obese patients with breast cancer.
Aim: To discriminate between fentanyl derivatives with high and low activities.
Methods: The support vector classification (SVC) method, a novel approach, was employed to investigate ...structure‐activity relationship (SAR) of fentanyl derivatives based on the molecular descriptors, which were quantum parameters including ΔE energy difference between highest occupied molecular orbital energy (HOMO) and lowest empty molecular orbital energy (LUMO), MR (molecular refractivity) and Mr (molecular weight).
Results: By using leave‐one‐out cross‐validation test, the accuracies of prediction for activities of fentanyl derivatives in SVC, principal component analysis (PCA), artificial neural network (ANN) and K‐nearest neighbor (KNN) models were 93%, 86%, 57%, and 71%, respectively. The results indicated that the performance of the SVC model was better than those of PCA, ANN, and KNN models for this data.
Conclusion: SVC can be used to investigate SAR of fentanyl derivatives and could be a promising tool in the field of SAR research.
Inhibition of diabetic nephropathy by a GH antagonist: A molecular analysis. Streptozotocin-treated C57B1/SJL mice developed glomerular hypertrophy and light microscopic lesions mimicking human ...diabetic glomerulosclerosis. In contrast, there were no glomerular hypertrophy and lesions in diabetic mice transgenic (TG) for a mutated growth hormone (bGH-G119K) that competes with native endogenous GH and results in dwarfism. We examined the molecular events underlying these findings. The non-transgenic (non-TG) diabetic mouse glomeruli had an increase in mRNA coding for α1IV collagen, laminin B1, TGF-β1, 72kDa collage-nase, and TIMP-3. In contrast, glomerular type IV collagen and laminin B1 mRNA levels were normal in diabetic TG dwarf mice. However, the 72kDa gelatinase, TIMP-3, and TGF-β1 mRNAs were elevated in the diabetic dwarfs. Type IV collagen and laminin accumulated in the glomeruli of diabetic non-TG, but not of diabetic dwarf mice, by immunofluorescence microscopy, confirming the mRNA data. GH binding protein mRNA levels were comparable in glomeruli from dwarf and non-TG mice, both diabetic and non-diabetic. We did not detect GH receptor mRNA in glomeruli. These data suggest that diabetic glomerulosclerosis is associated with an increase in type IV collagen and laminin synthesis, and that these changes do not occur in mice transgenic for bGH119K, a functional antagonist of GH. The increase of 72kDa gelatinase, TIMP-3, and TGF-β1 mRNAs, independent of GH, suggested that these changes induced by hyperglycemia were not sufficient for the induction of glomerulosclerosis.
To investigate structure-activity relationships of N-(3-Oxo-3,4-dihydro-2H-benzo1,4oxazine-6-carbonyl) guanidines in Na/H exchange inhibitory activities and probe into a new method of the ...computer-aided molecular screening.
The hyper-polyhedron model (HPM) was proposed in our lab.
The samples with probably higher activities could be determined in such a way that their representing points should be in the hyper-polyhedron region where all known samples with high activities were distributed. And the predictive ability of different methods available was tested by the cross-validation experiment.
The accurate rate of molecular screening of N-(3-Oxo-3,4-dihydro-2H-benzo1,4oxazine-6-carbonyl) guanidines by HPM was much higher than that obtained by PCA (principal component analysis) and Fisher methods for the data set available here. Therefore, HPM could be used as a powerful tool for screening new compounds with probably higher activities.
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