A miRNA-disease association prediction model based on tree-path global feature extraction and fully connected artificial neural network with multi-head self-attention mechanism.

BACKGROUND: MicroRNAs (miRNAs) emerge in various organisms, ranging from viruses to humans, and play crucial regulatory roles within cells, participating in a variety of biological processes. In numerous prediction methods for miRNA-disease associations, the issue of over-dependence on both similarity measurement data and the association matrix still hasn't been improved. In this paper, a miRNA-Disease association prediction model (called TP-MDA) based on tree path global feature extraction and fully connected artificial neural network (FANN) with multi-head self-attention mechanism is proposed. The TP-MDA model utilizes an association tree structure to represent the data relationships, multi-head self-attention mechanism for extracting feature vectors, and fully connected artificial neural network with 5-fold cross-validation for model training. RESULTS: The experimental results indicate that the TP-MDA model outperforms the other comparative models, AUC is 0.9714. In the case studies of miRNAs associated with colorectal cancer and lung cancer, among the top 15 miRNAs predicted by the model, 12 in colorectal cancer and 15 in lung cancer were validated respectively, the accuracy is as high as 0.9227. CONCLUSIONS: The model proposed in this paper can accurately predict the miRNA-disease association, and can serve as a valuable reference for data mining and association prediction in the fields of life sciences, biology, and disease genetics, among others.

TCM syndrome differentiation in colorectal cancer patients assisted by differences in gut microbiota: An exploratory study.

Objective: To explore the difference in gut microbiota between different traditional Chinese Medicine (TCM) syndromes in patients with colorectal cancer (CRC) and its internal relationship. Methods: From June 2020 to August 2021, 109 colorectal cancer patients with a clear pathological diagnosis who had not yet undergone surgery or chemotherapy were classified according to the TCM syndrome classification, and the feces samples of 109 patients with preoperative colorectal cancer were collected. 16s rRNA gene sequencing was used to determine gut microbiota diversity and abundance in CRC patients with different TCM syndrome, and LEfSe analysis was made to screen different TCM syndrome for differential representative microbiota. Results: 109 patients were divided into 5 syndromes by TCM syndrome classification, which were Liver and Kidney Yin Deficiency Syndrome (LKYDS, n = 19), Spleen Deficient Qi Stagnation Syndrome (SDQSS, n = 30), Stasis and Poison Obstruction Syndrome (SPOS, n = 17), Damp-Heat Syndrome (DHS, n = 30), Qi and Blood Deficiency Syndrome (QBDS, n = 13). Alpha diversity index showed significant differences among the five groups of TCM syndromes, with Shannon index being highest in the SDQSS group and lowest in the LKYDS (p = 0.003). ACE index being highest in the SDQSS group and lowest in the SPOS (p = 0.010). PD whole tree index being highest in the SDQSS group and lowest in the SPOS (p = 0.017). Similarly, beta diversity showed significant differences among the five groups of TCM syndromes, with principal coordinate analysis (PCo1 = 31.86 %, PCo2 = 5.62 %) showing separation and coincidence between the groups, and Adonis group differences showing coincidence between the QBDS-LKYDS (p = 0.702), QBDS-DHS (p = 0.133), and SDQSS-DHS (p = 0.260) groups. LEfSe analysis revealed that the representative microbiota of DHS patients was Dialister sp Marseille P5638 (LDA = 3.05, p＜0.001), the representative microbiota of SPOS patients was Oscillospirales (LDA = 4.78, p = 0.029), the representative microbiota of SDQSS patients was Selenomonadaceae (LDA = 3.94, p = 0.003), the representative microbiota of LKYDS patients was Dialister (LDA = 4.19, p = 0.001), and the representative microbiota of QBDS patients was Akkermansia muciniphila (LDA = 4.23, p = 0.006). Conclusions: There are significant differences in gut microbiota between different TCM syndromes in CRC patients. The five microbiota, Dialister sp Marseille P5638, Oscillospirales, Selenomonadaceae, Dialister, and Akkermansia muciniphila, may be differential markers of TCM syndrome in CRC and are expected to be one of the bases for accurate TCM syndrome differentiation of CRC.

IL-33 Suppresses the Progression of Atherosclerosis via the ERK1/2-IRF1-VCAM-1 Pathway.

PURPOSE: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism. METHODS: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E-/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1). RESULTS: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E-/- mice. CONCLUSION: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis.

Conduction system pacing for ventricular pacing requirement is feasible and effective on patients with hypertrophic cardiomyopathy and cardiac dysfunction.

Objective: We aimed to evaluate the feasibility and safety of his-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with hypertrophic cardiomyopathy (HCM) and heart failure (HF). Methods: Patients with HF and interventricular septal thickness (IVST) ≥ 13 mm resulted from HCM, who accepted conduction system pacing (CSP) with a percentage of ventricular pacing > 40% from May 2018 to April 2022 were consecutively enrolled in our center. LBBP was preferred and HBP was the alternative therapy unless IVST ≥ 16 mm or LBBP failed, whereas LBBP would be the alternative therapy if HBP failed in patients with IVST ≥ 16 mm. All patients were followed up for at least one year. Data including clinical, echocardiographic parameters and electrocardiogram measurements, were collected and evaluated in patients with and without left ventricular ejection fraction (LVEF) < 50%. Results: A total of 27 patients (65.93 ± 9.09 years old) were enrolled and only 3 patients failed in CSP (11.11%) via LBBP (6/13) and HBP (18/21) procedures. LVEF (P = 0.521), left ventricular end-diastolic diameter (LVEDD) (P = 0.816), and QRS duration (P = 0.928) did not worsen after CSP, and left atrial diameter (LAD) (49.58 ± 8.99 mm vs.47.04 ± 9.82 mm, P = 0.045) tended to improve slightly after 19.19 ± 7.71 months follow-up. Of note, LVEF (39.22%±7.51% vs. 45.22%±9.59%, P = 0.015), LVEDD (52.11 ± 10.10 mm vs. 48.33 ± 9.07 mm, P = 0.037), LAD (50.33 ± 8.93 mm vs. 46.11 ± 5.97 mm, P = 0.013) and New York Heart Association (NYHA) grade (2.67 ± 0.5 vs. 1.38 ± 1.02, P = 0.029) improved in 9 patients with LVEF < 50%, whereas LVEF (P = 0.372), LVEDD (P = 0.665), LAD (P = 0.093) and NYHA grade (P = 0.452) did not deteriorate in patients with preserved ejection fraction. Conclusion: CSP was safe and feasible in patients with HCM and cardiac dysfunction, and did not worsen cardiac performance especially in patients with LVEF < 50%. HBP might be an effective alternative to LBBP in patients with significantly thickened interventricular septum.

The value of multimodal functional magnetic resonance imaging in differentiating p53abn from p53wt endometrial carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is the sixth most common cancer in women. P53 gene expression in patients with endometrial cancer can predict the efficacy and prognosis of patients with neoadjuvant therapy. PURPOSE: To explore the value of multimodal magnetic resonance imaging (MRI) in differentiating p53 abnormal (p53abn) from p53 wild-type (p53wt) EC. MATERIAL AND METHODS: Data from 47 EC patients, including 14 p53abn cases and 33 p53wt cases, were retrospectively analyzed. The preoperative MRI sequences included amide proton transfer weighted (APTw) imaging, T2 mapping, mDIXON-Quant imaging and diffusion-weighted imaging (DWI). After post-processing, APT, T2, transverse relaxation rate (R2*), fat fraction (FF) and apparent diffusion coefficient (ADC) maps were obtained. The APT, T2, R2*, FF and ADC values for lesions of the two groups of cases were measured by two observers who were blind to the pathological data. RESULTS: The APT value and R2* value in the p53abn group were higher than those in the p53wt group, while the ADC value was lower (all P < 0.05). There was no statistically significant difference in T2 value and FF value between the two groups (all P > 0.05). The area under curve of APT, R2*, ADC and combined APT + R2*+ADC values for identification of p53abn and p53wt EC were 0.739, 0.689, 0.718 and 0.820, respectively (all P > 0.05). CONCLUSION: APTw, mDIXON-Quant and DWI techniques can be usedfor quantitative identification of p53abn and p53wt EC. The multimodal MRI provides a new way for preoperative quantitative evaluation of EC molecular typing, which has certain clinical application value.

Spatial distribution characteristics of sediment connectivity and soil erosion in small watershed in brown soil hilly region of low mountains in western Liaoning Province, China.

Understanding the spatial distribution characteristics of soil erosion and sediment connectivity is important for formulating integrated watershed management measures. Based on the InVEST sediment delivery ratio model, we used the connectivity index and soil loss model to measure the spatial distribution characteristics of sediment connectivity and soil erosion in Erdaoling watershed of brown soil hilly region of low mountains in western Liaoning. By exploring slope, aspect and land use characteristics under different sediment connectivity levels and soil erosion levels, we analyzed the relationships among topography, land use, sediment connectivity, and soil erosion. The results showed that the average sediment connectivity in the watershed was -3.79, and that the average soil erosion was 614 t·km2·a-1. High connectivity was mainly found in sloping farmland, while low connectivity was mainly found in forest and grassland. The soil erosion intensity of 93.3% of the watershed area was below moderate, with only 1.1% of the area being above extremely strong. The higher the sediment connectivity level, the higher the proportion of the area <5° slope, while the area proportion of the rest slope was relatively stable. The proportion of cultivated land area increased, while the proportion of forest and grassland land area decreased. The area proportion on negative slope decreased, while that on positive slope increased. With increasing soil erosion intensity, the area proportion of slope <8° increased and the area proportion of the rest slope was relatively stable. The proportion of forest and grassland area decreased, while the proportion of other land use area increased. The proportion of slope area on positive slope increased, while that on negative slope decreased. Land use was a key factor influencing the spatial response relationship between soil erosion and sediment connectivity in this watershed.

Study on the preparation and luminescence properties of SrGe4 O9 :Mn4+ red phosphors for plant illumination.

In this study, SrGe4 O9 :Mn4+ red phosphors for plant illumination were prepared using a high-temperature solid-phase method. The samples were characterized and analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), fluorescence spectroscopy, and other techniques. The phase structure, apparent morphology, and luminescence properties of the SrGe4 O9 :Mn4+ red phosphors were investigated. The results indicated that the dopant Mn4+ was incorporated into the matrix structure by substituting some Ge4+ ions without any changes in the crystal structure of the SrGe4 O9 matrix. The samples comprised micron-scale particles and exhibited high purity and uniform distribution of elements. The SrGe4 O9 :Mn4+ phosphors exhibited relatively strong red light emission at 660 nm under the excitation of a 430-nm blue light, and the luminescence intensity was the highest when the Mn4+ doping amount was 1%. Proper doping of Ti4+ or Sn4+ could effectively improve the luminescence intensity of the SrGe4 O9 :Mn4+ phosphors. The light-emitting diode (LED) device packaging showed that the SrGe4 O9 :Mn4+ red phosphors could be used for plant growth illumination.

Empirical analysis based on the related factors of college students' mental health problems.

Interpersonal relationship is one of the important factors affecting college students' mental health. The relationship between interpersonal relationship and college students' mental health has also become a large number of academic research topics. In order to explore whether there is a correlation between optimism and college students' mental health, and if so, what kind of situation it presents. Based on literature review, mathematical statistics and questionnaire survey, this study optimized the iterative process of clustering algorithm. Extract valuable parts from a large amount of precipitation of students' psychological data, establish data models, and provide decision-making guidance for managers. The results show that there are significant differences between optimists and pessimists in optimistic factors and pessimistic factors. Optimists score significantly higher on optimistic factors than pessimists, while pessimists score significantly lower than pessimists. Conclusion optimism can significantly alleviate life stress and intervene psychological crisis.

Impact of COVID-19 on the mental health of Singaporean GPs: a cross-sectional study.

BACKGROUND: COVID-19 has stressed healthcare systems and workers worldwide. GPs, as first points of contact between suspected cases and the healthcare system, have assumed frontline roles in this crisis. While the prevalence of mental health problems and illnesses arising in healthcare workers (HCWs) from tertiary care settings during the COVID-19 pandemic is well-examined,1 the impact on GPs remains understudied. AIM: To describe the prevalence and predictors of anxiety, burnout, depression, and post-traumatic stress disorder (PTSD) among GPs during the COVID-19 pandemic. DESIGN & SETTING: Survey of GPs operating in Singapore primary care clinics. METHOD: GPs completed a survey that comprised of four validated psychometric instruments. Open-ended questions asked about responders' challenges and their envisaged support. Data were analysed with multiple logistic regression with demographic data as covariates; concepts of grounded theory were used to analyse the qualitative responses. RESULTS: A total of 257 GPs participated. Fifty-five (21.4%) met the scales' criteria for anxiety, 211 (82.1%) for burnout, 68 (26.6%) for depression, and 23 (8.9%) for PTSD. Multivariate regression analysis showed working in a public primary care setting was associated with anxiety and depression. Qualitative analyses uncovered possible stressors: changes to clinical and operational practices; increased workloads; and financial difficulties. CONCLUSION: Mental health issues were found to be present in Singaporean GPs during the pandemic. Prevalence of anxiety, burnout, and depression were found to be higher than those reported pre-COVID-19. The findings also provide determinants of the issues that serve as possible foci for targeted interventions.

[Aqueous-phase Oxidation of Dissolved Organic Matter (DOM) from Extracts of Ambient Aerosols].

Recently, a large number of laboratory studies have focused on the aqueous-phase photochemistry of single organic compound in atmospheric condensed phases, yet few studies have been conducted on the aqueous-phase photochemical oxidation of real-world complex dissolved organic matter (DOM). Therefore, in this work, we report experimental results for the photochemical oxidation of DOM extracts from ambient fine aerosol samples upon direct photolysis or against OH oxidation, under both simulated sunlight and ultraviolet irradiation conditions. The products at different stages of photolysis were analyzed via UV-vis and spectroscopy and soot-particle aerosol mass spectrometry (SP-AMS) to investigate their optical and chemical characteristics. The results demonstrate the effective degradation of DOM under UV irradiation, and the f44 values of the corresponding products aremuch lower than under sunlight irradiation. A variety of carboxylic acids were generated during liquid-phase photolysis, and oxalic acid was found to be the most abundant. The light absorbance and concentration of HULIS did not change significantly under sunlight illumination; however, under UV and UV+·OH conditions, the concentration of HULIS increased continuously with reaction time. The HULIS concentration at 23 h was approximately four times the initial value, indicating the formation of brown carbon species with carboxyl, hydroxyl, and aromatic and other functional groups. Our results show that the increase in light absorptivity and formation rate of brown carbon from DOM are limited when aqueous-phase oxidation occurs under sunlight illumination. In comparison, DOM can constantly decompose into HULIS or small molecules under ultraviolet light illumination, and the light absorptivity of the remaining organic matter may be relatively high, resulting in final products with a high unit mass absorption efficiency (MAE). We have investigated the aqueous-phase oxidation of actual filter extracts for the first time, and our results provide valuable insights to the formation of air pollution complexes.

[Application research of entropy weight-based grey systematic theory in quality evaluation of Angelicae Sinensis Radix slices].

In order to discuss the "entropy weight method" for weighting various indicators in the comprehensive evaluation of Angelicae Sinensis Radix slices(ASR), the quality of ASR was comprehensively evaluated by entropy weight-based gray systematic theory and cluster analysis. In this study, the contents of ferulic acid, volatile oil, polysaccharide, alcohol extract, water extract, moisture, total ash and acid-insoluble ash in 44 batches of ASR from different sources were determined. The entropy weight method was used for objective weighting. With relative correlation(r_i) as a measure, a multi-index comprehensive evaluation model was constructed for the quality of ASR. The results showed that the relative correlation value of 44 batches of ASR ranged from 0.301 9 to 0.662 9. There were certain differences in the quality of ASR from different sources. The ASR S1-S8, traceable and standardized in processing techno-logy, showed a high relative correlation degree and high quality ranking, indicating that the implementation of systemic management of the production chain of Chinese herbal pieces was beneficial to the quality control of ASR. The quality evaluation results of 44 batches of ASR were consistent with those of traditional geo-authentic habitats for ASR and the mainstream varieties of ASR on market, and basically consistent with the results of cluster analysis. This study suggests that the gray systematic theory based on the entropy weighting method can be used for the quality evaluation of ASR. The objective weighting of the entropy weight method improves the reliability of the gray correlation method and the scientificity of ASR quality evaluation.

[Ecological stoichiometric characteristics of soil and microbial biomass C, N, P in rhizosphere soil of Paris polyphylla and Panax japonicus cultivated understory].

Comparison of total organic carbon(TOC), total nitrogen(TN), total phosphorus(TP), soil microbial biomass carbon(MBC), nitrogen(MBN), phosphorus(MBP) and their stoichiometric ratios measuring from understory planting of Paris polyphylla and Panax japonicus rhizosphere soil with the data of the original forest soil will help us to understand the influence of different planting patterns between soil traits and soil microbial interaction and nutrient cycle characteristics. The results showed that the contents of TOC, TN and MBN were the highest in the rhizosphere soil of P. japonicus, while the highest values of TP, MBC and MBP were found in the rhizosphere soil of P. polyphylla. The changes of TOC∶TN, TOC∶TP, TN∶TP, MBC∶MBN, MBC∶MBP and MBN∶MBP of P. polyphylla and P. japonicus rhizosphere soil compared with the data of the original forest soil were 3.65 and 37.32%,-14.89 and 82.23%,-17.87 and 32.76%, 25.67 and-50.60%,-75.95 and-16.33% as well as-80.79 and 69.76%, respectively. TN and TP were significantly correlated with MBN and MBP respectively. Although, monoculture of P. polyphylla and P. japonicus changed soil nutrient level, it did not reach the state of nutrient deficiency. The demands for nitrogen and phosphorus between P. polyphylla and P. japonicus were quite different. According to their different habits, monoculture of P. polyphylla and P. japonicus could change the understory soil traits, resulting in allometric changes in part of soil nutrient stoichiometry and soil microbial stoichiometry, and then the disappearance of internal stability. The variations in the understory soil caused by P. polyphylla and P. japonicus is developing in completely different directions, whether this phenomenon indicates that the two species have less niche overlap needs further study.

[Study on lipid production by reusing herb residues of Songling Xuemaikang Capsules].

Songling Xuemaikang Capsules is a Chinese patent medicine mainly made of the Chineses medicine Puerariae Lobatae Radix and leaves of Pinus massoniana. During its production, a large amount of herb extraction residues would be treated as wastes, resulting in resource wasting and serious environmental pollution. In order to solve this problem, we took the hydrolysates of Puerariae Lobatae Radix, P. massoniana leaves, and whole herb residues of Songling Xuemaikang Capsules as the fermentation substrate to explore the ability of Rhodosporidium toruloides to produce microbial lipid. The results showed that the R. toruloides could produce lipid with use of the residues from Songling Xuemaikang Capsules, and the lipid contents reached 33.6%. The lipid products had similar fatty acid composition profiles to those of vegetable oils. Herb residues were converted into fermentation substrates in this study, and were recycled into the production of high value-added compounds to realize the transformation of the wastes, laying the foundation for the sustainable utilization of herb residues.

Systematic Review and Meta-Analysis of Effects of Transfusion on Hemodynamic and Oxygenation Variables.

OBJECTIVES: RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding. DATA SOURCES: PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019. STUDY SELECTION: All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion. DATA EXTRACTION: Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients. DATA SYNTHESIS: We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were -0.0 L/min/m (-0.1 to 0.1 L/min/m) (p = 0.86) for cardiac index; -1.8 beats/min (-3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m (71.1-122.5 mL/min/m) (p < 0.01) for oxygen delivery index; 2.9% (2.2-3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; -3.7% (-4.4% to -3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m (0.9-9.0 mL/min/m) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m (2.3-14.5 mL/min/m; p = 0.01). CONCLUSIONS: Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis.

Serotypes and virulence genes of Pseudomonas aeruginosa isolated from mink and its pathogenicity in mink.

In this study, 20 P. aeruginosa strains were isolated from 112 farmed mink exhibiting hemorrhagic pneumonia in mideastern Shandong province, China. Serotype G (18/20) was the dominant serotype among the isolates with prevalence in mink, followed by serotype B (1/20), serotype C (1/20). The 9 virulence-associated genes of P. aeruginosa were tested using PCR. The prevalence of the virulence genes for the isolates were algD 95% (19/20), plcH 85% (17/20), exoY 80% (16/20), aprA 75% (15/20), lasB 70% (14/20), exoS 65% (13/20), exoT 60% (12/20) and toxA 60% (12/20), respectively. The 20 isolates were negative for exoU gene. The isolates exhibited multidrug resistance and cross resistance, using antimicrobial disc susceptibility assays. The animal experiments demonstrated that LD50% of the P.aeruginosa-CS-2 in the intratracheally challenged mink was 2.2 × 107.0 CFU, and 6.8 × 104.0 CFU in the intraperitoneally challenged mink. It implied that both the inoculation doses and the routes of inoculation could have influences on the pathogenicity of P. aeruginosa in mink. Therefore, the evolutionary and epidemiological surveillance of P. aeruginosa in mink should be further strengthened for public health.

[Development and model of health education and health promotion for schistosomiasis control in mountainous and hilly endemic areas].

Transmission control and interruption of schistosomiasis has been gradually achieved in the mountainous and hilly endemic areas with the implementation of the schistosomiasis control programmes, which are moving towards the progress of schistosomiasis elimination. As an important measure of schistosomiasis control, health education is experiencing new challenges and problems in the new situation, and conventional health education of schistosomiasis control has already failed to meet the needs of socioeconomic and cultural development and the increasing changes of human production and life styles in the endemic areas. Therefore, a precision health education model for schistosomiasis control is of great need to be established to highly effectively promote the implementation of schistosomiasis control measures. This review summarizes the important role of health education in schistosomiasis control in mountainous and hilly endemic areas, and describes the new health education model based on optimization of the policy environment and creation of the community atmosphere according to the changes in the endemic situation of schistosomiasis and requirements of the schistosomiasis control target, so as to promote the precision and sustainable implementation of health education and health promotion in schistosomiasis control.

[Construction and application of the surveillance system for schistosomiasis transmission risk in Sichuan Province].

OBJECTIVE: To build a schistosomiasis transmission risk surveillance system in Sichuan Province, so as to provide technical support for facilitating the progress towards schistosomiasis elimination in the province. METHODS: The surveillance sites for schistosomiasis transmission risk were assigned in 63 endemic counties (districts) of 11 cities (prefectures) in Sichuan Province. During the period from 2015 through 2018, wild feces contamination, the sources of Schistosoma japonicum infections (fever patients, livestock and wild animals), water infectivity in key settings, snail distribution in key settings, and snail breeding risk (snail importation and spread, floating debris carrying snails and snail breeding in ecological wetlands) were monitored in the surveillance sites. RESULTS: From 2015 to 2018, a total of 1 636 wild faces were detected in Sichuan Province, and 3 faces were positive for S. japonicum, with a 0.18% positive rate; among 3 995 livestock and 59 wild mice monitored, no S. japonicum infection was detected. A total of 49 414 fever patients were monitored in 2018, and 493 were seropositive for S. japonicum infection; then, 445 seropositives were subjected to stool examinations, and no egg-positives were found. From 2010 to 2018, a total of 93 sentinel sites were assigned, and 3 994 sentinel mice were placed for monitoring the water infectivity, with one S. japonicum-infected mouse detected. Between 2015 and 2018, a total of 4 156 key settings were investigated covering an area of 1 998.46 hm2, and 668 settings were detected with snails (16.07%), covering an area of 193.26 hm2; 497 suspected settings with a likelihood of snail importation with plant introduction were monitored from 2017 to 2018, and 65 settings with snails were found with 2 673 snails captured; 593 sites were assigned to collect the floating debris from 2017 to 2018, and 9 191.39 kg floating debris were collected with 186 snails captured; 4 wetlands were monitored for the risk of schistosomiasis transmission from 2013 to 2015, and snail breeding was found in 2 wetlands. No S. japonicum infection was identified in snails captured from all surveillance sites. CONCLUSIONS: A sensitive and effective schistosomiasis transmission risk surveillance system has been successfully established in Sichuan Province. There is still a risk of schistosomiasis transmission risk in local areas of Sichuan Province. Therefore, the integrated schistosomiasis control measures with emphasis on the control of the source of S. japonicum infections should be further intensified, and snail monitoring and control and monitoring and control of schistosomiasis in wetlands should be also intensified.

Overexpression of a Novel Cytochrome P450 Promotes Flavonoid Biosynthesis and Osmotic Stress Tolerance in Transgenic Arabidopsis.

Flavonoids are mainly associated with growth, development, and responses to diverse abiotic stresses in plants. A growing amount of data have demonstrated the biosynthesis of flavonoids through multienzyme complexes of which the membrane-bounded cytochrome P450 supergene family shares a crucial part. However, the explicit regulation mechanism of Cytochrome P450s related to flavonoid biosynthesis largely remains elusive. In the present study, we reported the identification of a stress-tolerant flavonoid biosynthetic CtCYP82G24 gene from Carthamus tinctorius. The transient transformation of CtCYP82G24 determined the subcellular localization to the cytosol. Heterologously expressed CtCYP82G24 was effective to catalyze the substrate-specific conversion, promoting the de novo biosynthesis of flavonoids in vitro. Furthermore, a qRT-PCR assay and the accumulation of metabolites demonstrated that the expression of CtCYP82G24 was effectively induced by Polyethylene glycol stress in transgenic Arabidopsis. In addition, the overexpression of CtCYP82G24 could also trigger expression levels of several other flavonoid biosynthetic genes in transgenic plants. Taken together, our findings suggest that CtCYP82G24 overexpression plays a decisive regulatory role in PEG-induced osmotic stress tolerance and alleviates flavonoid accumulation in transgenic Arabidopsis.

Application of multiple chemical and biological approaches for quality assessment of Carthamus tinctorius L. (safflower) by determining both the primary and secondary metabolites.

BACKGROUND: The florets of Carthamus tinctorius L. (safflower) serve as the source of a reputable herbal medicine targeting gynecological diseases. Conventional investigations regarding the quality control of safflower, however, mainly focused on the secondary metabolites with primary metabolites ignored. PURPOSE: To holistically evaluate the quality difference of safflower samples collected from five different producing regions by multiple chemical and biological approaches with both the primary and secondary metabolites considered. METHODS: A precursor ions list-triggered data-dependent MS2 approach was established by ultra-high performance liquid chromatography/Q-Orbitrap mass spectrometry (UHPLC/Q-Orbitrap MS) to comprehensively identify the secondary metabolites from safflower. Primary metabolites were identified by various 1D and 2D nuclear magnetic resonance (NMR) experiments. Similarity evaluation and quantitative assays of all the characterized primary metabolites and a quinochalcone C-glycoside (QCG) marker, hydroxysafflor yellow A (HSYA), were performed by quantitative 1H NMR (qNMR) using an external standard method. Multiple in vitro models with respect to the antioxidant, anti-platelet aggregation, and antioxidant stress injury effects, were assayed to determine the efficacy differences. RESULTS: Totally thirteen primary metabolites (including one nucleoside, two sugars, five organic alkali/acids, and five amino acids) and 135 secondary metabolites (97 QCGs and 38 flavonoids) could be identified or tentatively characterized from safflower. Good chemical consistency was observed between the commercial safflower samples and a standard safflower sample, with similarity varying in the range of 0.95‒0.99. The results from qNMR-oriented quantitative experiments (thirteen primary metabolites and HSYA) and biological assays indicated the quality of safflower samples from Xinjiang (XJ-2 and XJ-4), Hunan (HuN-1 and HuN-2), and Sichuan (SC), was comparable to the standard safflower sample. CONCLUSION: The integration of multiple chemical (using two analytical platforms, UHPLC/Q-Orbitrap MS and NMR) and biological (four in vitro models) approaches by determining both the primary and secondary metabolites demonstrated a powerful strategy that could facilitate the holistic quality evaluation of traditional Chinese medicine.

Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway.

BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. METHODS: Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. RESULTS: EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. CONCLUSION: EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway.