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In response to the issues in the teaching of the medicinal chemistry course, we propose an innovative teaching approach based on a higher-order skills-oriented advanced research-oriented learning model. By combining the P-MASE research-oriented learning model with advanced instructional activity design, we create a higher-order skills-oriented teaching activity that integrates "interesting case research + creative research activities + project challenges", and construct a teaching scenario that incorporates the instructional content. Under the guidance of teachers, students advance their research-oriented learning in medicinal chemistry through the P-MASE framework, which involves problem identification, method exploration, scientific analysis, effective solution, and evaluation of outcomes. This approach facilitates theoretical development and enhances students' research and innovation thinking skills. Through an analysis of the achievement of the medicinal chemistry course, it is confirmed that this model can effectively enhance the higher-order nature, innovation, and challenge of the course. [ABSTRACT FROM AUTHOR]

Objective *To analyze the whole-brain inputs to the projection neurons in the lateral dorsal nucleus (LD) of thalamus innervating primary visual cortex (V1) in mice. Methods * The adeno-associated virus (AAV) vectors expressing the fusion protein of wheat germ agglutinin and Cre recombinase (Cre) were injected into V1 of C57BL/6J male mice, and the AAV vectors with Cre-inducible expression of avian sarcoma/leukosis virus envelope glycoprotein receptor TVA and rabies glycoprotein were injected into LD, respectively. Twenty-eight days later, the pseudotyped rabies virus (RV) was injected into V1. After the full expression of RV-mediated green fluorescent protein in the infected input neurons of LD, i.e., 7 d later, brain samples were collected and frozen sections were made. The whole-brain distribution of RV-labeled neurons were observed under fluorescence microscope, and quantitative analysis was performed by using high-throughput anatomical data analysis software. Results * Through fluorescence microscope and quantitative analysis, the whole-brain map showed that the inputs of LD neurons innervating V1 mainly came from cortex, middle brain and inter brain, accounting for (58.1±4.8)%, (23.2±0.9)% and (15.3±4.0)% of the total number of GFP-labeled neurons in the whole brain, respectively. In the cortex, the areas with the most input neurons were somatomotor area, visual area and somatosensory area. A large number of input neurons were also distributed in prefrontal cortex and medial commissural cortex. In the sensory cortex, the cell bodies of the inputs were mainly distributed in the fifth and sixth layers. Conclusion* The direct inputs of LD neuron subgroups innervating V1 in mice are widely distributed throughout the brain, most of which are located in the cortex. [ABSTRACT FROM AUTHOR]

Objective. To explore the inhibitory effect of superoxide dismutase (SOD) on the formation of semen-derived enhancer of viral infection (SEVI) amyloid fibrils. Methods. Prostatic acid phosphatase 248-286 (PAP248-286) at 440 µmol/L or seminal fluid was incubated with SOD at different activity levels, and at different time points, aliquots were taken from each sample for thioflavin T (ThT) staining, circular dichroism (CD) and transmission electron microscope (TEM) to detect the effect of SOD on the formation of SEVI. The effect of SOD on the ability of SEVI to promote human immunodeficiency virus-1 (HIV-1) infection was detected by virus infection enhancement experiment. The effects of inactivated SOD on the formation of SEVI and the ability of SEVI to promote virus infection were also detected. The SOD activity levels in the semen of five healthy volunteers were detected by using total SOD activity detection kit. Results. The results of ThT staining showed that 46 U/mL and 92 U/mL SOD could inhibit the formation of SEVI fibrils in the PAP248-286 solution in vitro at 48-h time point. The results of CD showed that SOD could inhibit the formation of β -sheet structure of SEVI. The results of TEM also showed that SOD could inhibit the formation of SEVI. The ThT staining in the semen also demonstrated the inhibitory effect of SOD on the formation of SEVI. As shown in the virus infection enhancement experiment, SOD could inhibit the promoting effect of SEVI on HIV-1 infection. When SOD was inactivated, the effects above almost disappeared. The SOD activities in the semen of the five healthy males were 74.87, 68.69, 85.46, 113.29, and 109.53 U/mL, respectively. Conclusion. SOD can inhibit the formation of SEVI fibrils in vitro and the promoting effect of SEVI on HIV-1 infection. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumor (pNET) is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is stiil the optimal treatment for resectable, well - differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis. [ABSTRACT FROM AUTHOR]

Based on the higher-order ionospheric corrections model, the impact magnitude of higher-order ionospheric delay on GPS observables was determined. Then, GPS data from 104 globally distributed IGS stations spanning the years 1999 to 2003 were reprocessed to study the effects of higher-order ionospheric corrections on GPS reference frame realization and site coordinates using GAMIT with state of the art models according to the 2010 IERS conventions. We compared the differences generated when applying different geomagnetic models to higher-order delays. Results show that both the reference frame origin and scale are influenced by the higher-order corrections, especially for the Z translation, which can add up to 20 mm, while the X and Y translation had a relatively smaller difference, less than 5 mm. Higher-order ionospheric effects can result in regional bias phenomenon at stations. Differences in the geomagnetic model lead to a change of up to 10 mm for the Z translation. Notable coordinate differences are found in some areas, these results are analyzed and discussed. [ABSTRACT FROM AUTHOR]

Objective To investigate the predictive value of CHADS2 and CHA2DS2-VASc score in left atrial (LA) or left atrial appendage (LAA) thrombus in patients with non-valvular atrial fibrillation (AF). Methods A total of 164 consecutive non-valvular AF patients confirmed by transesophageal echocardiography (TEE) were included in this study, and were divided into two groups, LA/LAA thrombus group and non LA/LAA thrombus group. The previous history was recorded in two groups of patients. Their CHADS2 and CHA2DS2-VASC scores were calculated based on the general data of two groups. The laboratory examinations and TEE indexes were compared between two gropes. Results Of all patients, the rate of LA/LAA thrombus was 19.5%. The CHADS2 and CHA2DS2-VASC scores were significantly higher in LA/LAA thrombus group than those of non LA/LAA thrombus group (2.1±1.3 vs 1.0±0.9, 3.4±1.8 vs 1.9±1.4, P<0.01). There were 13(11.9%) and 5 (8.8%) patients showed LA/LAA thrombus under low-moderate risk in the two score systems, respectively. Multivariate logistic regression analysis showed that CHADS2 score ≥2 points(OR=3.735, 95% CI: 1.508-9.251, P=0.004) and CHA2DS2-VASc score ≥2 points (OR=5.104, 95% CI: 1.586-16.425, P=0.006) were independent risk factors of LA/LAA thrombus. ROC curve showed that AUC of CHADS2 and CHA2DS2-VASc scores to predict LA/LAA thrombus were 0.731 (95%CI:0.630- 0.832, P<0.001) and 0.742 (95% CI: 0.640-0.843, P<0.001), respectively. Conclusion CHADS2 and CHA2DS2-VASC score ≥2 points are independent risk factors of LA/LAA thrombus in patients with non-valvular atrial fibrillation. The predictive values of both score systems are moderate. There are also LA/LAA thrombus in low-moderate risk patients when using the two score systems, and with the increased risk stratification, the rate of LA/LAA thrombus is increased. [ABSTRACT FROM AUTHOR]