Application of mobile medical intelligence software combined with OBE-CBCL dual-track teaching method in standardized training of orthopaedic residents / 沈阳医学院学报

Objective:To explore the effect of mobile medical intelligent software combined with OBE-CBCL dual-track teaching method in standardized training of orthopaedic residents.Methods:The orthopedic residents who received resident standardized training in our hospital from Jan 2022 to Sep 2022 were selected as the study subjects.The orthopedic residents who received regular teaching method from Jan 2022 to Mar 2022 were group A,orthopedic residents who received mobile medical intelligent software + regular teaching method from Apr 2022 to Jun 2022 were group B,and the orthopedic residents who received mobile medical intelligent software + OBE-CBCL dual-track teaching method from Jul 2022 to Sep 2022 were group C.All three groups participated in the relevant professional theoretical knowledge assessment,Mini-CEX,and satisfaction survey at the time of discharge.Results:The scores of professional theoretical knowledge assessment in groups B and C were higher than that in groups A,and it was higher in group C than that in group B(P＜0.05).The scores of each item of Mini-CEX in groups B and C were higher than those in group A(P＜0.05).Except for clinical judgment ability,the scores of the other items of Mini-CEX in group C was higher than those in group B(P＜0.05).In the satisfaction survey,the scores of deepening knowledge mastery in groups B and C were higher than that in group A,and that in group C was higher than that in group B(P＜0.05).The scores of improving clinical thinking and stimulating learning interest in groups B and C were higher than those in group A(P＜0.05),and the scores of improving team assistance and overall satisfaction in group C were higher than those in groups A and B(P＜0.05).Conclusion:Mobile medical intelligent software combined with OBE-CBCL dual-track teaching can significantly improve teaching effect of orthopaedic resident standardized training.

Estudio computacional de las interacciones moleculares entre el timol y los residuos HIS41 y CYS145 presentes en el sitio activo de la proteasa 3CLpro

La proteína proteasa 3CLpro del SARS-CoV-2 es una enzima crucial para la replicación viral, razón por la cual se convierte en un blanco terapéutico de gran importancia. El timol (2-isopropil-5-me-tilfenol), un compuesto natural que se encuentra en el tomillo (Thymus vulgaris), exhibe potencial actividad antiviral contra la proteasa 3CLpro. En este estudio, usando acoplamiento molecular con AutoDockTools-1.5.6, se evaluaron las energías de interacción molecular entre el timol y los residuos de aminoácidos en el sitio activo de la proteína proteasa 3CLpro. Luego, con la teoría cuántica de Átomos en Moléculas (QTAIM) y la de Interacciones no covalentes (NCI) se analizaron los tipos de interacciones moleculares entre los residuos de aminoácidos identificados y el timol. Los cálculos cuánticos se llevaron con el software Orca-5.0.3, utilizando el método DFT con el funcional M06-2X y el conjunto base aug-cc-pVDZ en fase gaseosa. Los resultados de acoplamiento molecular indican que el timol se une a la proteína 3CL con una energía de interacción igual a -3,784 kcal/mol. El análisis QTAIM indica la presencia de puntos críticos de enlace entre el timol y los residuos HIS41 y CYS145. Además, se observa la formación de un enlace de hidrógeno entre el grupo OH del timol y el residuo CYS145, lo cual es corroborado por los análisis ELF (Electron Localization Function) y NCI (Non Covalent Interactions). Finalmente, el método NCI confirma la presencia de interacciones de Van der Waals con el residuo HIS41. Los resultados sugieren que el mecanismo de inhibición de la actividad de la proteína 3CLpro es controlado por interacciones moleculares tipo puente de hidrógeno e interacciones débiles.

The protease 3CLpro of the SARS-CoV-2 is a crucial enzyme for viral replication, becoming a highly important therapeutic target. Thymol (2-isopropyl-5-methyl-phenol), a naturally occurring compound found in thyme, exhibits potential antiviral activity against the 3CLpro protease. In this study, using molecular docking with AutoDockTools-1.5.6, the molecular interaction energies between thymol and amino acid residues in the active site of the protein protease 3CLpro were evaluated. Then, with the Atoms in Molecules (QTAIM) and Non-covalent Interactions (NCI) theories, the types of molecular interactions between identified amino acid residues and thymol were analyzed. Quantum calculations were carried out with the Orca-5.0.3 software using the DFT method with the M06-2X functional and the aug-cc-pVDZ basis set in the gas phase. The molecular docking results indicate that thymol is linked to the 3CL protein with an interaction energy equal to -3.784 kcal/mol. QTAIM analysis indicates the presence of critical binding sites between thymol and residues HIS41 and CYS145. In addition, the formation of a hydrogen bond between the OH group of thymol and the CYS145 residue is observed, which is corroborated by the ELF and NCI analyses. Finally, the NCI method confirms the presence of Van der Waals interactions with the HIS41 residue. The results suggest that the mechanism of inhibition of the activity of the 3CLpro protein is controlled by molecular interactions such as hydrogen bonding and weak interactions.

A protease 3CLpro do SARS-CoV-2 é uma enzima crucial para a replicação viral, tornando-se um alvo terapêutico de grande importÅncia. O timol (2-isopropil-5-me-tilfenol), um composto natural encontrado no tomilho, exibe potencial atividade antiviral contra a protease 3CLpro. Neste estudo, utilizando o docking molecular com o AutoDockTools-1.5.6, foram avaliadas as energias de interação molecular entre o timol e os residuos de aminoácidos no sítio ativo da proteína protease 3CLpro. Em seguida, com a teoria quantica de atomos em moleculas (QTAIM) e da interacões no-covalentes (NCI), foram analisados os tipos de interações moleculares entre os resíduos de aminoácidos identificados e o timol. Os cálculos quÅnticos foram realizados com o software Orca-5.0.3 usando o método DFT com o funcional M06-2X e a base aug-cc-pVDZ definida na fase gasosa. Os resultados do docking molecular indicam que o ti-mol está ligado à proteína 3CL com uma energia de interação igual a -3.784 kcal/ mol. A análise QTAIM indica a presença de sítios de ligação críticos entre o timol e os resíduos HIS41 e CYS145. Além disso, observa-se a formação de uma ponte de hidrogênio entre o grupo OH do timol e o resíduo CYS145, o que é corroborado pelas análises ELF e NCI. Finalmente, o método NCI confirma a presença das interações de Van der Waals com o resíduo HIS41. Os resultados sugerem que o mecanismo de inibição da atividade da proteína 3CLpro é controlado por interações moleculares como ligações de hidrogênio e interações fracas.

Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

The clinical significance of CX3CL1 in primary Sj?gren′s syndrome complicated with interstitial lung disease / 中华风湿病学杂志

Objective:To investigate the clinical significance of CX3CL1 in pSS-ILD.Methods:A total of 103 pSS patients treated in the Department of Rheumatology and Immunology of the Affiliated Hospital of Guilin Medical College from December 2019 to December 2020 were included (42 cases with ILD and 61 cases without ILD), and 46 healthy physical check-up subjects in the health check-up center of the Affiliated Hospital of Guilin Medical college were included as controls. Demographic data, clinical manifestations, clinical parameters, lung function test, lung HRCT and serum samples of enrolled patients were collected. The serum levels of CX3CL1 and KL-6 in PSS-ILD patients, pSS patients and healthy subjects were detected by ELISA, and the correlation between CX3CL1 and clinical related indexes in pSS-ILD and pSS patients was analyzed. Independent sample t test, Kruskal-Wallis H test, Pearson correlation and Logistic regression analysis were used for statistical analysis. Results:As KL-6, the levels of CX3CL1 were significantly higher in the pSS-ILD group compared to both the pSS and control groups [CX3CL1: 9.08 (3.97, 30.56)ng/ml, 8.12 (6.16, 8.89)ng/ml, and 7.09 (5.86, 9.07)ng/ml, H=3.53, P=0.019; KL-6: 19.08 (8.05, 24.72)mU/ml, 15.9 (4.52, 19.26)mU/ml, 12.74 (8.09, 16.23) mU/ml, H=9.85, P=0.008]. Furthermore, CX3CL1 was shown to be positively correlated with KL-6( r=0.82, P<0.001). The cutoff value for CX3CL1 was determined to be at a concentration of 9.07 ng/ml with a specificity of 86.9% and sensitivity of 43.6%. The area under the receiver operating characteristic curve was 0.603. CX3CL1 exhibited significant correlations with predcited carbon monoxide dispersion as a percentage of expected value ( r=-0.45, P=0.004), HRCT score ( r=0.54, P<0.001), pulmonary hypertension ( r=0.37, P=0.039), ESSDAI score ( r=0.36, P=0.049), as well as chest tightness and acute breath (coefficient of association r=0.49, P<0.001). Conclusion:The level of serum CX3CL1 is directly proportionate to the severity of KL-6, pulmonary fibrosis, and lung function impairment, thereby suggests that CX3CL1 can be utilized as a parameter for the diagnosis and assessment of pSS-ILD.

Chemokine CX3CL1 has potential anti-fibrosis effect in mouse liver fibrosis / 基础医学与临床

Objective To explore the effect and mechanism of chemokine CX3CL1 on mouse liver fibrosis model.Methods C57BL/6 mice were randomly divided into CCl-4 model group and normal control group with 8 animals in each group.The model group was injected with 10%CCl-4 intra peritoneally for 6 weeks.After 6 weeks,the mice were sacrificed,and the pathological changes of the mouse liver were observed by HE staining.The level of CX3CL1 in peripheral blood of the mice was measured,and the expression level of CX3CL1 mRNA in the liver tis-sue of the mice was detected.In addition,in order to explore the mechanism of CX3CL1,the level of IFN-γ in mouse serum was detected as well.Results After the 6-week modeling,the liver pathology microscopy showed a successful modeling of liver fibrosis.The serum CX3CL1 level and liver tissue CX3CL1 expression in the model group were found to be significantly up-regulated,which suggested a potential impact on the pathogenesis of liver fi-brosis.In addition,the level of IFN-γ in the serum of mice in the model group increased significantly.Conclusions CX3CL1 is related to liver fibrosis in mice,and its mechanism might be explained by promoting the production of IFN-γ so to prevent liver fibrosis.

The predictive value of SAA and NLR for adverse pregnancy outcomes in patients with severe preeclampsia treated by multidisciplinary team / 中华急诊医学杂志

Objective:To evaluate the predictive value of serum amyloid A (SAA) and neutrophil-lymphocyte ratio (NLR) for adverse pregnancy outcomes in patients with severe preeclampsia treated by multidisciplinary team.Methods:A total of 105 patients with severe preeclampsia admitted to the ICU of Hangzhou First People's Hospital from October 2014 to July 2022 were retrospectively enrolled. They were divided into the adverse pregnancy outcome group ( n = 62) and the non-adverse pregnancy outcome group ( n = 43) according to the pregnancy outcome. SAA, NLR and other laboratory indicators and related clinical data of all patients were collected within 24 h after admission. The general clinical data of the two groups were compared, and multivariate Logistic regression analysis was used to find the risk factors affecting adverse pregnancy outcome of patients with severe preeclampsia. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SAA and NLR for adverse pregnancy outcomes in patients with severe preeclampsia treated by multidisciplinary team. Results:The ICU length of stay [4.00 (3.00, 5.00) vs. 3.00 (3.00, 4.00), P=0.022], acute physiology and chronic health evaluationⅡ (APACHEⅡ) score [9.00 (7.00, 11.25) vs. 7.00 (5.00, 9.00), P=0.002], white blood cell count [(12.29±4.25) vs. (10.41±4.00), P=0.025], SAA [37.85 (11.00, 72.83) vs. 9.00 (8.00, 20.70), P<0.001] and NLR [7.95 (5.22, 12.37) vs. 5.20 (3.25, 8.77), P=0.002] in the adverse pregnancy outcome group were higher than those in the non-adverse pregnancy outcome group. The gestational weeks [30.00 (26.75, 31.00) vs. 33.00 (32.00, 35.00), P<0.001], direct bilirubin [2.10 (1.50, 2.50) vs. 2.20 (1.90, 4.60), P=0.019] and alkaline phosphatase (99.00 (74.00, 124.25) vs. 133.00 (95.00, 188.00), P<0.001] levels in the adverse pregnancy outcome group were significantly lower than those in the non-adverse pregnancy outcome group ( P<0.05). Multivariate Logistic regression analysis showed that earlier gestational weeks ( OR=0.564, 95% CI: 0.408-0.780, P<0.001), higher SAA ( OR=1.028, 95% CI: 1.002-1.055, P=0.036) and APACHE Ⅱ score ( OR=1.282, 95%CI: 1.048-1.569, P=0.016) were the risk factors affecting adverse pregnancy outcomes in patients with severe preeclampsia. The area under the curve of SAA, NLR and SAA, NLR combined with APACHE Ⅱ score were 0.770, 0.678, and 0.844, respectively. The combined prediction efficiency of SAA, NLR and APACHE Ⅱ score was higher than that of single prediction ( P<0.05). Conclusions:SAA and NLR have good predictive efficacy for adverse pregnancy outcomes in patients with severe preeclampsia treated by multidisciplinary team. The predictive efficacy of SAA and NLR combined with APACHE Ⅱ score is higher than that of single index.

Assessment Of Gingival Phenotype At The Aesthetic Zone In A Malay Population Using Probe Test

@#Introduction: The gingival phenotype (GP) of teeth at the aesthetic zone often influences dental rehabilitation plans and treatment outcomes. This study aimed to assess the prevalence of GP in the Malay population in relation to gender and age. Methods: The GP of 100 patients were determined using the Probe test method. Other clinical parameters were assessed include crown width/crown length (CW/CL) ratio, tooth morphology and width of keratinised tissue. Periodontal parameters were assessed by two calibrated examiners. Data were analysed using descriptive statistics, one-way ANOVA and Kruskal-Wallis test. Results: A higher prevalence of thick GP was found at the maxilla for both genders, whereas a thin phenotype was observed at the mandible. At maxilla, both thick and thin GP were found in all age groups, while the mandible showed a higher prevalence of thin GP. Significant differences in GP were found between males and females for mandibular and maxillary anterior teeth and the mandibular lateral incisor (p<0.05), while no significant difference was found for other parameters assessed; age group, CW/CL, tooth morphology and WKT. Conclusion: Thicker GP is more prevalent in male population and at maxillary anterior. Mandibular anterior GP presented commonly with a thin GP regardless of gender or age-group.

Control of sodium and potassium homeostasis by renal distal convoluted tubules

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

El mejillón Semimytilus patagonicus (Mytilida: Mytilidae) y el gusano Pseudonereis gallapagensis (Phyllodocida: Nereididae) como herramientas ecotoxicológica para la contaminación por detergentes en ambientes marinos / The mussel Semimytilus patagonicus (Mytilida: Mytilidae) and the worm Pseudonereis gallapagensis (Phyllodocida: Nereididae) as ecotoxicological tools for detergent pollution in marine environments

Introduction: The bivalve Semimytilus patagonicus is a potentially useful bioindicator because of its feeding mechanism, and the worm Pseudonereis gallapagensis is also interesting as a bioindicator because it is benthonic, abundant, and a food source for the squid Doryteuthis gahi. However, their sensitivity to contaminants has not been sufficiently studied. Objective: To test the usefulness of the mussel Semimytilus patagonicus and the polychaete Pseudonereis gallapagensis as ecotoxicological tools for detergents in the marine environment. Methods: We used 120 individuals of S. patagonicus from Miraflores and 120 of P. gallapagensis from Barranco (both near the city of Lima, Peru). For the bioassays, we used two anionic detergents (active ingredient, ai, Sodium Dodecylbenzene Sulfonate). For S. patagonicus, with an average valve length of 32.3 ± 6.4 mm, we tested "Double power Ariel®" (90 %) at concentrations of 17.5, 35, 70 and 140 mg ai l-1, evaluated after 48 and 72 h of exposure; and for P. gallapagensis, with a total body length of 20.4 ± 8.8 mm, we tested "Caricia®" at 62.5, 125, 250, 500 and 1 000 mg of ai l-1 at 24, 48 and 72 h of exposure. Results: The LC50 values (Mean Lethal Concentration) were 34.95 mg ia l-1 for S. patagonicus and 102.48 mg ia l-1 for P. gallapagensis at 72 h of exposure. The detergents were toxic for S. patagonicus and slightly toxic for P. gallapagensis. The risk classification for S. patagonicus is "harmful" and for P. gallapagensis "not classifiable". Conclusions: These two bioindicators allow evaluating the acute toxicity of SDBS-based commercial detergents in the marine aquatic environment.

Introducción: El bivalvo Semimytilus patagonicus es un bioindicador potencialmente útil por su mecanismo de alimentación, y el gusano Pseudonereis gallapagensis también es interesante como bioindicador por ser bentónico, abundante y fuente de alimento para el calamar Doryteuthis gahi. Sin embargo, su sensibilidad a los contaminantes no ha sido suficientemente estudiada. Objetivo: Probar la utilidad del mejillón S. patagonicus y el poliqueto P. gallapagensis como herramientas ecotoxicológicas para detergentes en el medio marino. Métodos: Se utilizaron 120 individuos de S. patagonicus de Miraflores y 120 de P. gallapagensis de Barranco (ambos cerca de la ciudad de Lima, Perú). Para los bioensayos se utilizaron dos detergentes aniónicos (ingrediente activo, ia, dodecilbenceno sulfonato de sodio). Para S. patagonicus, con una longitud valver promedio de 32.3 ± 6.4 mm, probamos Ariel Doble Poder® (90 %) a concentraciones de 17.5, 35, 70 y 140 mg·ia·l-1, evaluadas a las 48 y 72 h de exposición; y para P. gallapagensis, con una longitud corporal total de 20.4 ± 8.8 mm, probamos Caricia® a 62.5, 125, 250, 500 y 1 000 mg·ia·l-1 a las 24, 48 y 72 h de exposición. Resultados: Los valores de CL50 (Concentración Letal Media) fueron de 34.95 mg·ia·l-1 para S. patagonicus y 102.48 mg·ia·l-1 para P. gallapagensis a las 72 h de exposición. Los detergentes fueron tóxicos para S. patagonicus y levemente tóxicos para P. gallapagensis. La clasificación de riesgo para S. patagonicus es "nocivo" y para P. gallapagensis "no clasificable". Conclusiones: Estos dos bioindicadores permiten evaluar la toxicidad aguda del detergente comercial a base de SDBS en el ambiente acuático marino.

Multi-level scoring approach to discover multi-targeting potency of medicinal plant phytochemicals against protein targets in SARS-CoV-2 and human ACE-2 receptor

SARS-CoV-2 pandemic has become a major threat to human healthcare and world economy. Due to the rapid spreading and deadly nature of infection, we are in a situation to develop quick therapeutics to combat SARS-CoV-2. In this study, we have adopted a multi-level scoring approach to identify multi-targeting potency of bioactive compounds in selected medicinal plants and compared its efficacy with two reference drugs, Nafamostat and Acalabrutinib which are under clinical trials to treat SARS-CoV-2. In particular, we employ molecular docking and implicit solvent free energy calculations (as implemented in the Molecular Mechanics -Generalized Born Surface Area approach) and QM fragmentation approach for validating the potency of bioactive compounds from the selected medicinal plants against four di?erent viral targets and one human receptor (Angiotensin-converting enzyme 2 -ACE-2) which facilitates the SARS-CoV-2entry into the cell. The protein targets considered for the study are viral 3CL main protease (3CLpro), papain-like protease (PLpro), RNA dependent RNA polymerase (RdRp), and viral spike protein-human hACE-2 complex (Spike:hACE2)including human protein target (hACE-2). Herein, thereliable multi-level scoring approach was used to validate the mechanism behind the multi-targeting potency of selected phytochemicals from medicinal plants. The present study evidenced that the phytochemicals Chebulagic acid, Stigmosterol, Repandusinic acid and Geranin exhibited efficient inhibitory activity against PLpro while Chebulagic acid was highly active against 3CLpro. Chebulagic acid andGeranin also showed excellent target specific activity against RdRp.Luteolin, Quercetin, Chrysoeriol and Repandusinic acid inhibited the interaction of viral spike protein with human ACE-2 receptor. Moreover Piperlonguminine and Piperine displayed significant inhibitory activity against human ACE-2 receptor. Therefore, the identified compounds namely Chebulagic acid, Geranin and Repandusinic acid can serve as potent multi-targeting phytomedicine for treating COVID-19

Development Of Halosulphate Based Phosphors And It's Applications

Synthesis and characterization of halosulphate-based phosphors is important for thermoluminescence dosimetry (TLD), radiophotoluminescence dosimetry (RPL) and scintillator materials. The enhancement of luminescence output in halosulphate-based phosphors and it may be useful for lamp, solid-state lamp and radiation. Dosimetry by activator as well as sensitizer are well known properties. The combustion technique is not applicable for the synthesis of TLD phosphors due to very fine particles, which show less TL intensity, while sol-gel, solid-state diffusion, melt method and precipitation methods are applicable for TLD phosphors. Two halosulphates namely Na21( SO4 ) 7 F6 Cl and 2K3Ca2(SO4)3F were prepared and doped with Dy and Tm for different concentration .Halosulphate , Na21( SO4 ) 7 F6 Cl was prepared by wet chemical method and Halosulphate , 2K3Ca2(SO4)3F was prepared by solid state diffusion method . The characterization was done by X - ray diffraction ( XRD ) , Thermo luminescence (TL) was also studied . For Dy doped Na21( SO4) 7 F6 Cl , The peak was observed at 1200 C and shoulder at 1750C for 0.2 % molar concentration of Dy. and for 2K3Ca2(SO4)3F doped with Tm the shoulder peak was observed at 240 0 C and at 150 0C for 0.7 % molar concentration of Tm.

Apigenin Induces Apoptosis of Human Colorectal Cancer CL187 Cells via PI3K/Akt and MAPK Signaling Pathways / 中国实验方剂学杂志

ObjectiveTo study the effect of apigenin on the proliferation and apoptosis of human colon cancer CL187 cells and the underlying mechanisms. MethodHuman colorectal cancer CL187 cells were treated with different concentrations of apigenin （0， 30， 45， 60 mg·L-1） according to the results of the preliminary experiment. The proliferation of CL187 cells was detected by methyl thiazolyl tetrazolium （MTT） and colony formation assays， and the apoptosis was observed via Hoechst 33258 staining. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of cysteine protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the CL187 cells treated with apigenin. Western blot was employed to measure the protein levels of Caspase-3， Bcl-2， and Bax associated with apoptosis， protein kinase B （Akt） and phosphorylated Akt （p-Akt） in phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway， and extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （MAPK）， and p-p38 MAPK protein in MAPK pathway. ResultCompared with the blank group， the apigenin groups had low cell survival rates and high inhibition rates on cell proliferation （P<0.01）. Apigenin decreased the cell clone number and clone formation rate， and increased the inhibition rate on clone formation （P<0.01）. After CL187 cells were treated with different concentrations of apigenin for 48 h， typical apoptosis characteristics such as nuclear pyknosis， chromatin condensation， and enhanced fluorescence reaction were observed. Compared with blank group， 45， 60 mg·L-1 apigenin treatments down-regulated the mRNA level of anti-apoptotic gene Bcl-2 （P<0.01） and all the apigenin treatments up-regulated those of the pro-apoptotic genes Bax and Caspase-3 （P<0.05， P<0.01）. Similarly， apigenin treatments down-regulated the protein level of Bcl-2 （P<0.05， P<0.01） and up-regulated those of Caspase-3 （P<0.05， P<0.01） and Bax （P<0.01， 45， 60 mg·L-1）. The blank group had higher protein level of Akt than the 60 mg·L-1 apigenin group （P<0.01）， higher protein levels of p-Akt， ERK1/2， and p-ERK1/2 than the 45， 60 mg·L-1 apigenin groups （P<0.01）， and higher protein levels of JNK and p-JNK than the apigenin groups （P<0.05， P<0.01）. Compared with blank group， 60 mg·L-1 apigenin up-regulated the protein level of p38 MAPK （P<0.05）， and all the apigenin groups up-regulated that of p-p38 MAPK （P<0.01）. Furthermore， apigenin lowered the p-Akt/Akt ratio （P<0.05， P<0.01） and p-ERK1/2/ERK1/2 ratio （P<0.01）， while it increased the p-JNK/JNK ratio （45， 60 mg·L-1； P<0.05， P<0.01） and p-p38 MAPK/p38 MAPK ratio （P<0.05， P<0.01）. ConclusionApigenin can inhibit the proliferation and promote the apoptosis of CL187 cells by inhibiting the PI3K/Akt signaling pathway and regulating the expression of proteins in the MAPK signaling pathway.

Apigenin Induces Apoptosis of Human Colorectal Cancer CL187 Cells via PI3K/Akt and MAPK Signaling Pathways / 中国实验方剂学杂志

ObjectiveTo study the effect of apigenin on the proliferation and apoptosis of human colon cancer CL187 cells and the underlying mechanisms. MethodHuman colorectal cancer CL187 cells were treated with different concentrations of apigenin （0， 30， 45， 60 mg·L-1） according to the results of the preliminary experiment. The proliferation of CL187 cells was detected by methyl thiazolyl tetrazolium （MTT） and colony formation assays， and the apoptosis was observed via Hoechst 33258 staining. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of cysteine protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the CL187 cells treated with apigenin. Western blot was employed to measure the protein levels of Caspase-3， Bcl-2， and Bax associated with apoptosis， protein kinase B （Akt） and phosphorylated Akt （p-Akt） in phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway， and extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （MAPK）， and p-p38 MAPK protein in MAPK pathway. ResultCompared with the blank group， the apigenin groups had low cell survival rates and high inhibition rates on cell proliferation （P<0.01）. Apigenin decreased the cell clone number and clone formation rate， and increased the inhibition rate on clone formation （P<0.01）. After CL187 cells were treated with different concentrations of apigenin for 48 h， typical apoptosis characteristics such as nuclear pyknosis， chromatin condensation， and enhanced fluorescence reaction were observed. Compared with blank group， 45， 60 mg·L-1 apigenin treatments down-regulated the mRNA level of anti-apoptotic gene Bcl-2 （P<0.01） and all the apigenin treatments up-regulated those of the pro-apoptotic genes Bax and Caspase-3 （P<0.05， P<0.01）. Similarly， apigenin treatments down-regulated the protein level of Bcl-2 （P<0.05， P<0.01） and up-regulated those of Caspase-3 （P<0.05， P<0.01） and Bax （P<0.01， 45， 60 mg·L-1）. The blank group had higher protein level of Akt than the 60 mg·L-1 apigenin group （P<0.01）， higher protein levels of p-Akt， ERK1/2， and p-ERK1/2 than the 45， 60 mg·L-1 apigenin groups （P<0.01）， and higher protein levels of JNK and p-JNK than the apigenin groups （P<0.05， P<0.01）. Compared with blank group， 60 mg·L-1 apigenin up-regulated the protein level of p38 MAPK （P<0.05）， and all the apigenin groups up-regulated that of p-p38 MAPK （P<0.01）. Furthermore， apigenin lowered the p-Akt/Akt ratio （P<0.05， P<0.01） and p-ERK1/2/ERK1/2 ratio （P<0.01）， while it increased the p-JNK/JNK ratio （45， 60 mg·L-1； P<0.05， P<0.01） and p-p38 MAPK/p38 MAPK ratio （P<0.05， P<0.01）. ConclusionApigenin can inhibit the proliferation and promote the apoptosis of CL187 cells by inhibiting the PI3K/Akt signaling pathway and regulating the expression of proteins in the MAPK signaling pathway.

Screening of the ubiquitin-proteasome system activators for anti-Alzheimer's disease by the high-content fluorescence imaging system / 中国天然药物

Ubiquitin-proteasome system (UPS) plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The discovery of UPS activators for anti-neurodegenerative diseases is becoming increasingly important. In this study, we aimed to identify potential UPS activators using the high-throughput screening method with the high-content fluorescence imaging system and validate the neuroprotective effect in the cell models of AD. At first, stable YFP-CL1 HT22 cells were successfully constructed by transfecting the YFP-CL1 plasmid into HT22 cells, together with G418 screening. The degradation activity of the test compounds via UPS was monitored by detecting the YFP fluorescence intensity reflected by the ubiquitin-proteasome degradation signal CL1. By employing the high-content fluorescence imaging system, together with stable YFP-CL1 HT22 cells, the UPS activators were successfully screened from our established TCM library. The representative images were captured and analyzed, and quantification of the YFP fluorescence intensity was performed by flow cytometry. Then, the neuroprotective effect of the UPS activators was investigated in pEGFP-N1-APP (APP), pRK5-EGFP-Tau P301L (Tau P301L), or pRK5-EGFP-Tau (Tau) transiently transfected HT22 cells using fluorescence imaging, flow cytometry, and Western blot. In conclusion, our study established a high-content fluorescence imaging system coupled with stable YFP-CL1 HT22 cells for the high-throughput screening of the UPS activators. Three compounds, namely salvianolic acid A (SAA), salvianolic acid B (SAB), and ellagic acid (EA), were identified to significantly decrease YFP fluorescence intensity, which suggested that these three compounds are UPS activators. The identified UPS activators were demonstrated to clear AD-related proteins, including APP, Tau, and Tau P301L. Therefore, these findings provide a novel insight into the discovery and development of anti-AD drugs.

TOXICIDAD AGUDA DEL HERBICIDA PARAQUAT EN Oreochromis niloticus (CICHLIDAE) Y Macrobrachium olfersii (PALAEMONIDAE) / Paraquat's herbicide acute toxicity in Oreochromis niloticus (Cichlidae) and Macrobrachium olfersii (Palaemonidae)

RESUMEN El Paraquat es un herbicida utilizado en la actividad agropecuaria para controlar hierbas, su modo de acción es por medio de contacto y no selectivo. Debido a su alta solubilidad en agua y baja volatilidad representa un riesgo potencial para organismos acuáticos, principalmente los que son cultivados con aguas superficiales que reciben impacto de la actividad agrícola. La tilapia Oreochromis niloticus y el langostino Macrobrachium olfersii son organismos de importancia comercial para la industria acuícola del estado de Veracruz, México. El objetivo de este estudio fue determinar la Concentración Letal Media (CL50) del herbicida Dasurquat® (ingrediente activo Paraquat) a través de un bioensayo de toxicidad aguda (96 horas). Se utilizaron como especímenes de prueba a juveniles de tilapia O. niloticus (peso promedio = 10 mg, longitud total= 8,75 mm) y otro el ensayo fue con poslarvas de langostino M. olfersii (peso promedio = 5 mg, longitud total= 5,72 mm). Se emplearon cinco concentraciones (5, 10, 20, 40 y 80 μL-1 para el bioensayo con juveniles de tilapia; para el bioensayo con poslarvas de langostino las concentraciones fueron 0,1, 0,2, 0,5, 0,7 y 1 μL-1). El diseño experimental consideró un control negativo, con dos repeticiones y dos réplicas por cada tratamiento. El análisis de datos se realizó con el método Probit para determinar la CL50 a 96 horas, se obtuvo un valor para juveniles de O. niloticus de 17,49 μL-1 con intervalo de confianza (95 %) con límite inferior de 13,75 μL-1 y límite superior 22,25 μL-1, para las larvas de M. olfersii se obtuvo un valor de 0,31 μL-1 con intervalo de confianza (95 %) con límite inferior de 0,26 μL-1 y límite superior 0,35 μL-1. El análisis de varianza demostró que no existió diferencia estadística significativa (p > 0.05) entre las réplicas de los tratamientos. Se concluye que es necesario continuar con estudios para evaluar su toxicidad en organismos acuáticos debido al amplio uso de este herbicida en la actividad agropecuaria, y determinar su riesgo para otras actividades productivas además de la acuicola.

ABSTRACT Paraquat is an herbicide used in the agricultural industry for weed and undergrowth control, its mode of action is by contact and nonselective. Due to its high-water solubility and low volatility, it represents a potential risk for non-target organisms. Oreochromis niloticus tilapia and the prawn Macrobrachium olfersii are important commercial species for Veracruz's aquaculture industry. The objective of this study was to determine the Mean Lethal Concentration (LC50) of the herbicide Dasurquat® (active ingredient Paraquat) through an acute toxicity bioassay (96 hours). Juvenile O. niloticus (average weight = 10 mg, total length = 8.75 mm) and juvenile M. olfersii postlarvae (average weight = 5 mg, total length = 5.72mm) were used as test specimens. Five herbicide concentrations (5, 10, 20, 40 and 80 μL-1 for tilapia and 0.1, 0.2, 0.5, 0.7 y 1 μL-1 for prawn) were applied. The experimental design considered a negative control, with two replications and two replicates for each treatment. Probit analysis determined that the LC50 at 96 hours for O. niloticus was 17.49 μL-1, with a lower 95 % confidence limit of 13.75 μL-1 and an upper limit of 22.25 μL-1, whereas for M. olfersii the LC50 at 96 hours was 0.31 μL-1, with a lower 95 % confidence limit of 0.26 μL-1 and an upper limit of 0.35 μL-1. The analysis of variance showed that there was no significant statistical difference (p > 0.05) between the replicates of the treatments. It is concluded that it is necessary to continue evaluating its toxicity in aquatic organisms due to the wide use of this herbicide in Veracruz's agricultural activity, to determine its potential risk to other activities.

Effect of CX3CL1/CX3CR1 in cerebral ischemia and its mechanisms / 国际脑血管病杂志

CX3CL1, also known as Fractalkine, is the only member of chemokines CX3C subclass. It plays an important role in a variety of central nervous system diseases and ischemic cerebrovascular diseases by binding to its specific receptor CX3CR1. In recent years, a large number of studies have investigated the specific role and related molecular mechanism of CX3CL1/CX3CR1. This article reviews the effect and molecular mechanism of CX3CL1/CX3CR1 in ischemic cerebrovascular disease, aiming to expand the understanding of the mechanism of CX3CL1/CX3CR1, and provide new ideas and intervention targets for the prevention, diagnosis and treatment of ischemic cerebrovascular disease.

Overexpression of a fusion protein of 4-coumaroyl-CoA ligase and polyketide synthase for raspberry ketone production in Chlamydomonas reinhardtii / 生物工程学报

Raspberry ketones have important therapeutic properties such as anti-influenza and prevention of diabetes. In order to obtain raspberry ketone from Chlamydomonas reinhardtii, two enzymes catalyzing the last two steps of raspberry ketone synthesis, i.e. 4-coumaryl-CoA ligase (4CL) and polyketide synthase (PKS1), were fused using a glycine-serine-glycine (GSG) tripeptide linker to construct an expression vector pChla-4CL-PKS1. The fusion gene 4CL-PKS1 driven by a PSAD promoter was transformed into a wild-type (CC125) and a cell wall-deficient C. reinhardtii (CC425) by electroporation. The results showed the recombinant C. reinhardtii strain CC125 and CC425 with 4CL-PKS1 produced raspberry ketone at a level of 6.7 μg/g (fresh weight) and 5.9 μg/g (fresh weight), respectively, both were higher than that of the native raspberry ketone producing plants (2-4 μg/g).

Research advances of chemokine receptor CX3CR1 and microglia in retinal degenerative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration are the main clinical blinding eye diseases with complex etiology and irreversible damage to vision. CX3CR1 is a specific receptor of the chemokine CX3CL1. Both of them participate in various physiological functions and pathological changes of the whole body through regulating the immune system of the body. In recent years, studies have pointed out that CX3CR1 regulates the activity and function of retinal microglia, which play an important role in the process of retinal degenerative diseases. In this paper, the structure and function of the chemokine receptor CX3CR1 and the role of microglia in retinal degenerative diseases were reviewed, so as to provide ideas and directions for future research and treatment of such diseases.

Molecular mechanism of Bufei Huoxue Capsule on COVID-2019 based on network pharmacology and molecular docking / 中草药

Objective: To explore the potential mechanism of Bufei Huoxue Capsule (BHC) on coronavirus disease 2019 (COVID-19), and provide a theoretical basis for the clinical application of BHC. Methods: TCMSP, BATMAN-TCM, CNKI and Pubmed databases were used to search the compounds and targets of BHC and GeneCards database was used to search the targets of COVID-19; The intersection method was used to obtain the targets related to the therapeutic effect of BHC. Cytoscape 3.7.2 software was applied for the construction of CMM-compounds-targets network map. Protein-protein interaction (PPI) network was constructed by STRING database. Gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis were conducted by DAVID. AutoDock Tools 1.5.6 and AutoDock vina 1.1.2 were used for molecular docking. Results: A total of 32 potential active components were screened from BHC, corresponding to 203 targets. Among them, there were 11 core compounds and 52 core targets. PPI network analysis showed that there were 25 key targets intervening COVID-19 by BHC. A total of 251 biological processes (P < 0.05) and 93 pathways (P < 0.05) were obtained by GO analysis and KEGG analysis, respectively. The results of molecular docking showed that the key compounds had good affinity with SARS-CoV-2 3CL hydrolase and angiotensin converting enzyme II. Conclusion: The active compounds of BHC can target IL6, MAPK8, PTGS2, PTGS1 and NCOA2 to regulate multiple signal pathways, and play a therapeutic role in the recovery period of COVID-19.

Mechanism of sovereign medicines in Sanren Decoction on COVID-19 based on network pharmacology and molecular docking / 中草药

Objective: To investigate the mechanism of sovereign medicines in Sanren Decoction on coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking methods. Methods: The main active ingredients of sovereign medicines in Sanren Decoction (Armeniacae Semen Amarum, Amomun kravanh Pierre ex Gagnep, and Coicis Semen) were obtained and screened from by TCMSP and TCMID V2.0, combined with related research. Using UniPort database to query the target proteins corresponding to the active ingredients, then a component-target network was constructed by Cytoscape 3.7.2. PPI network was constructed through the STRING website, and cytoHubba was used to analysis the key subnetworks. CTD database was used to analyze GO and KEGG enrichment of the active ingredient target proteins of Sanren Decoction. Using the active ingredients of sovereign medicines in Sanren Decoction and related chemical drugs such as lopinavir as ligands, molecular docking with the SARS-CoV-2 3CL hydrolase was performed through the CB-Dock website. Results: Sovereign medicines in Sanren Decoction had 39 active ingredients, corresponding to 168 target proteins. The GO enrichment analysis obtained 25 biological processes (BP) items, 14 related items of cell composition (CC), and two molecular function (MF) item, respectively. KEGG enrichment screened 36 signaling pathways such as innate immune system, cytokine signaling in immune system, signaling by interleukins. The molecular docking results suggested that the active ingredients of mairin, ziziphin_qt, and oleanolic acid of sovereign medicines in Sanren Decoction had good binding energy with SARS-CoV-2 3CL hydrolase, and the Vina score of them were similar to those of lopinavir (the 3CLpro inhibitor) and remdesivir (RNA-dependent RNA polymerase inhibitor). Conclusion: Sovereign medicines in Sanren Decoction may participate in inflammation-related signaling pathways by regulating inflammatory factors, regulating multiple physiological processes of the disease with multi-components, multi-targets, and multi-pathways. It plays a certain intervention role in the treatment of COVID-19 and its active ingredients have potential resistance to SARS-CoV-2.