Life Satisfaction and Its Relationship With Personality Traits Among Medical College Students in China.

BACKGROUND: Life satisfaction is a comprehensive psychological index to measure a person's life quality. Previous studies have found that population sociological factors, physiological factors, psychological factors, and social factors all affect life satisfaction, but few studies have looked at the role of stable psychological factors, such as personality, in life satisfaction. Thus, this study combined previous research results and theories to study the current situation of college students' life satisfaction and its correlation with personality. OBJECTIVE: This study aims to comprehensively assess the life satisfaction levels among university students enrolled in a medical college in China, explore their correlation with various demographic factors and personality traits, identify potential areas for intervention, and provide recommendations for improving students' overall well-being and fostering the development of a positive and healthy personality. METHODS: A stratified cluster sampling method was used to select college students from a university. The questionnaire consists of general characteristics, a life satisfaction scale, and the Big Five Inventory. Descriptive statistical methods were conducted to describe the college students' life satisfaction status; an analysis of variance was performed to compare the score of life satisfaction among different demographic features; and the correlation between the score of life satisfaction and the Big Five Inventory was also analyzed. RESULTS: A total of 3116 subjects were included in this survey. The life satisfaction of females was higher than that of males in the dimensions of family, friends, school, and overall satisfaction (p<0.05). The life satisfaction of males in the self dimension was higher than that of females (p<0.05). The life satisfaction of different weight types had statistical significance in the life dimension (p<0.05). The life satisfaction of family, school, and overall well-being among smoking college students was lower than that of non-smoking college students (p<0.05). The life satisfaction of non-drinking college students in family, friends, life, school, and overall life satisfaction scores was higher than those of drinking college students (p<0.05). College students who get plenty of sleep a day (more than eight hours) scored higher life satisfaction scores in the self dimension than sleep-deprived college students (p<0.05). In addition to the family dimension, students taking long physical exercise breaks every day had higher life satisfaction scores in every dimension than students lacking physical exercise (p<0.05). The mean score of personality in the agreeableness and openness dimensions is the highest. Correlation analysis showed that the personality score in each dimension was positively correlated with the life satisfaction score in each dimension except for the neuroticism dimension of personality (p<0.05). CONCLUSION: The life satisfaction of college students is different for different lifestyles. The student management department should pay attention to the physical and mental health of college students with low life satisfaction and further find out the reasons for the difference in life satisfaction. Meanwhile, education should be strengthened for college students and encourage them to give up smoking and alcohol; strengthen physical training; and university education should strengthen the personality cultivation of college students.

Analysis of risk factors and prognosis of diarrhea after renal transplantation.

BACKGROUND: Diarrhea is a prevalent complication after renal transplantation. OBJECTIVE: To examine the risk factors for diarrhea after renal transplantation, evaluate their combined predictive values, and analyze the prognosis. METHODS: Clinical data of patients who underwent allogeneic renal transplantation in the Second People's Hospital of Shanxi Province from January 2019 to March 2020 were retrospectively analyzed, cases were screened and grouped, independent risk factors for diarrhea after renal transplantation were analyzed by univariate analysis and multivariate analysis, and their predictive value was evaluated by receiver operating characteristic (ROC) curve. The survival time of recipient grafts in diarrhea and non-diarrhea groups were evaluated by Kaplan-Meier and log-rank test. RESULTS: We included 166 recipients in the study and the incidence of diarrhea was 25.9%; univariate and logistic regression multivariate analyses revealed that independent risk factors for diarrhea in recipients were that the type of renal transplant donor was DCD (donation after circulatory death), immunity induction was onducted with basiliximab + antithymocyte globulin (ATG), and ATG alone, the type of mycophenolic acid (MPA) used was mycophenolate mofetil capsules, and delayed graft function (DGF) occurred after transplantation. The ROC curve indicated that the combination of the four factors had good accuracy in predicting the occurrence of diarrhea in recipients. The graft survival rate two years after the operation in the diarrhea group was significantly lower than that in the non-diarrhea group. CONCLUSION: Diarrhea affected the two-year survival rate of the graft. The type of donor, immunity induction scheme, and the type of MPA and DGF were independent risk factors for diarrhea in recipients, and the combination of the four factors had good prognostic prediction value.

Human midbrain dopaminergic progenitors.

Human midbrain dopaminergic progenitors (mDAPs) are one of the most representative cell types in both basic research and clinical applications. However, there are still many challenges for the preparation and quality control of mDAPs, such as the lack of standards. Therefore, the establishment of critical quality attributes and technical specifications for mDAPs is largely needed. "Human midbrain dopaminergic progenitor" jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human mDAPs in China. This standard specifies the technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for human mDAPs, which is applicable to the quality control for human mDAPs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will facilitate the institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human mDAPs for clinical development and therapeutic applications.

Chronotypes and their association with sleep quality among Chinese college students of Anhui Province: a cross-sectional study.

OBJECTIVES: To describe the prevalence of chronotype and sleep quality among Chinese college students and explore the relationship between chronotype and sleep quality. DESIGN: A cross-sectional study. SETTING: Four colleges and universities in Anhui, China, between November and December 2020. PARTICIPANTS: A total of 4768 college students were recruited using a stratified, multistage, cluster sampling survey. OUTCOME MEASURES: Morningness-Eveningness Questionnaire 19 was used to determine the chronotype of the students and the Pittsburgh Sleep Quality Index (PSQI) was used to measure their sleep quality. The multiple logistic regression model was used to explore the potential association between chronotype and sleep quality. RESULTS: The self-reported proportions of evening-type (E-type), neutral-type and morning-type among college students were 51.17%, 45.14% and 3.69%, respectively. The mean PSQI score was 4.97±2.82 and the prevalence of poor sleep quality was 18.2%. After adjusting the covariates by multiple logistic regression analysis, E-type was positively associated with subjective sleep quality (OR=1.671, 95% CI 1.414 to 1.975), sleep latency (OR=1.436, 95% CI 1.252 to 1.647), sleep duration (OR=2.149, 95% CI 1.506 to 3.067), habitual sleep efficiency (OR=1.702, 95% CI 1.329 to 2.180), daytime dysfunction (OR=1.602, 95% CI 1.412 to 1.818) and overall poor sleep quality (OR=1.866, 95% CI 1.586 to 2.196). CONCLUSIONS: College students mainly exhibited E-type, and an elevated prevalence of poor sleep quality existed among these students. The E-type was positively associated with poor sleep quality.

Real-world treatment patterns and survival for locally advanced esophageal squamous cell carcinoma.

The "real world" treatment mode and clinical efficacy of locally advanced esophageal squamous cell carcinoma (LAESCC) are unclear. Meanwhile, the role of immunotherapy in the clinical practice is also puzzling. We conducted the research to investigate the statue of "real world" LAESCC. The clinical data of patients with locally advanced esophageal squamous cell carcinoma which met the criteria from January 2010 to December 2019 have been retrospectively analyzed, and the distribution of clinical treatment patterns has been analyzed. They cover such aspects as dfferences in survival time and further analysis of the differences in overall survival (OS) and progression-free survival (PFS) between patients who received immunotherapy and those who did not receive immunotherapy. What is more, Cox risk regression model has also been used to evaluate the risk factors affecting the prognosis of LAESCC. The cases of a total of 5328 newly diagnosed patients with esophageal cancer were collected, and a total of 363 patients were included in the study, with a median age of (46.2 ± 7.8) years old; 84 (23.1%) and 279 (76.9%) patients received 1L and ≥ 2L, respectively; Concurrent chemoradiotherapy (74.1%) and paclitaxel combined with platinum-based chemotherapy (14.3%) were the main first-line treatment options; fluorouracil combined with cisplatin regimen-based chemotherapy (63.8%) was the main treatment option for ≥ 2L, of which 69 patients (25.3%) received immunization treatment; OS of patients with 1 line of therapy and ≥ 2L were (22.4 ± 7.2) months and (38.7 ± 8.5) months, respectively, and the comparison between groups was statistically significant (P < .05); among 69 patients with ≥ 2L who received immunotherapy, PFS and The OS was (14.6 ± 6.9) and (45.3 ± 9.7) respectively, and the comparison between the groups was statistically significant (all P < .05). Cox multivariate analysis has shown that clinical stage, immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are the main factors affecting OS. and immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are independent factors affecting PFS. Concurrent chemoradiotherapy is currently one of the standard treatments for LAESCC, and most patients are still willing to receive second-line or above treatments. Adding immunotherapy to standard treatment modalities may further optimize clinical treatment modalities and improve patient outcomes.

Association of learning environment and self-directed learning ability among nursing undergraduates: a cross-sectional study using canonical correlation analysis.

OBJECTIVES: This study explores the relationship between the perception of the learning environment and self-directed learning (SDL) ability among nursing undergraduates. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study was conducted in December 2020 with 1096 junior and senior undergraduate nursing students (aged 16-22) from Wannan Medical College in Anhui Province, China. OUTCOME MEASURES: The Chinese version of the Dundee Ready Educational Environment Measure questionnaire and a validated Chinese version of college students' SDL ability scale were used to assess students' perceptions about their learning environment and their SDL ability. Canonical correlation analysis was performed to evaluate their correlation. RESULTS: The total score for the learning environment was 120.60 (scoring rate: 60.30%), and the score for SDL ability was 89.25 (scoring rate: 63.75%). Analysis indicated that the first canonical correlation coefficient was 0.701 and the contribution rate was 94.26%. The perception of the learning environment was mainly determined by students' perception of learning (SPL) and academic self-perceptions (SASP), with SDL ability mainly determined by self-management ability and cooperative learning ability. SPL and SASP were positively correlated with self-management ability and cooperative learning ability. Multiple linear regression analysis revealed that SPL, SASP, students' perceptions of atmosphere and students' social self-perceptions had a significant impact on SDL ability. CONCLUSIONS: The SDL ability of nursing undergraduates was not high. SPL and SASP were positively correlated with self-management ability and cooperative learning ability. Nursing educators can improve students' SDL ability by changing their learning environment, using, for example, new student-centred teaching methods.

Associations between Chinese college students' anxiety and depression: A chain mediation analysis.

OBJECTIVE: Anxiety and depression are great public health concerns among college students. The purpose of this study was to explore whether sleep quality and quality of life (QoL) play mediating roles in anxiety and depression among Chinese college students. METHOD: A total of 2757 college students (mean age = 19.07; SD = 1.14) completed the questionnaires, including a brief demographic survey. The 2-item General Anxiety Disorder (GAD-2) and the 2-item Patient Health Questionnaire (PHQ-2) were used to assess the symptoms of anxiety and depression, respectively. And the Pittsburgh Sleep Quality Index (PSQI) and the Short-Form 36 Health Survey (SF-36) were used to evaluate college students' sleep quality and QoL, respectively. Mediation analyses were conducted by using PROCESS macro in the SPSS software. RESULT: Anxiety had both direct and indirect effects on depression. Sleep quality and QoL were not only independent mediators in the relationship between anxiety and depression but also chain mediators. CONCLUSION: The results of the current study highlight the crucial role of early intervention for depression with a focus on college students with anxiety, more especially, on those with poorer sleep quality and lower QoL.

Effectiveness of seminar-case learning for use in practice teaching of statistics for undergraduates majoring in preventive medicine: a prospective cluster-randomized controlled trial.

BACKGROUND: The seminar-case learning (SCL) method is a case-oriented teaching model, with teachers and students as the main body of teaching, characterized by communication, interaction, and mutual inspiration. This study explored the effects of the SCL method versus traditional lecture-based learning (LBL) in the statistics curriculum for undergraduate students majoring in preventive medicine. Research questions were: 1) whether the scores of students in the experimental group (the SCL model) were higher than those in the control group (the LBL model); 2) whether the students' satisfaction in the experimental group was better than that in the control group; and 3) whether the self-report benefit of students in the experimental group was better than that in the control group. METHODS: We conducted a two-armed cluster-randomized education intervention trial in practice teaching of health statistics among undergraduates majoring in preventive medicine. Two administrative classes (classes 1-4 and classes 5-8) were divided into the experimental group and the control group according to the principle of drawing lots. The students in two groups received the same statistical theory course. For the arrangement of statistical practice course, the experimental group adopted the SCL model, and the control group used the LBL model. The teaching effect was evaluated via an examination and an anonymous questionnaire survey. RESULTS: Scores for noun explanation questions in the experimental group showed no statistical significance with that of the control group(U = 2911.0, P = 0.964). The scores of single choice, calculation, and case analysis questions, and the total scores were significantly higher than that of the control group (P < 0.05). Students' satisfaction with arrangements of the practice course in the experimental group (92.41%) was significantly higher than that of in the control group (77.03%), the difference was statistically significant (χ2 = 7.074, P = 0.008). The self-report benefit of students in the experimental group was better than that in the control group (P < 0.05). CONCLUSION: As an effective method of high-quality education, the SCL model is worthy of further promotion in the practice teaching of preventive medicine.

The Association of Suicidal Ideation With Family Characteristics and Social Support of the First Batch of Students Returning to a College During the COVID-19 Epidemic Period: A Cross Sectional Study in China.

Objective: To investigate the prevalence of suicidal ideation among the first batch of students returning to a college during the COVID-19 epidemic, and to explore the correlation of suicidal ideation with family characteristics and social support. Methods: A cluster sampling survey with a self-designed questionnaire was conducted among the first batch of students returning to a college in Wuhu, China. The Positive and Negative Suicidal ideation (PANSI) and Social Support Scale (SSRS) were used to define students' suicidal ideation and social support, respectively. The influence of family characteristics and social support on the students' suicidal ideation was investigated using multivariate unconditional logistic regression analysis. Results: Two thousand seven hundred valid questionnaires were collected, including 673 males (24.9%) and 2,027 females (75.1%), in this study. A total of 146 students (5.4%) showed suicidal ideation. Male respondents reported higher rates (7.9%) than females (4.6%). Multivariate logistic regression analysis showed that a higher risk level of residence before returning to school and lower objective support were the risk factors for suicidal ideation in males. In contrast, a higher level of maternal education, a poorer relationship with the mother, and lower scores for subjective support and support availability had significant effects on females' suicidal ideation. Limitations: This is a cross-sectional study, and lacks comparison to the time point unaffected by COVID-19. Moreover, it was limited by COVID-19 epidemic prevention and control restrictions, and the differences in returning to school in different regions. Only one college was investigated in this study, and all of the respondents were sophomores, so there may be some limitations in the representativeness of the sample and extrapolation of the results. Conclusion: Family characteristics and social support have had an important influence on suicidal ideation among students returning to school during the COVID-19 epidemic. Some gender differences were identified. Targeted interventions are needed for early prevention and control.

Obesity related microRNA­424 is regulated by TNF­α in adipocytes.

In recent years, obesity has become a major public health concern. Obesity has been previously associated with low­grade inflammation and TNF­α induction in adipose tissue, which subsequently disrupts adipocyte metabolism. MicroRNAs (miRNAs/miRs) are important metabolic factors and their dysregulation has been associated with obesity­related metabolic syndromes. In fact, it has been directly suggested that miR­424 may be functionally associated with adipogenesis, although its exact role in this process remains unclear. The present study aimed to identify the function of miR­424 in adipogenesis. In the present study, miR­424 expression levels were analyzed during adipogenesis and the differential expression of this miRNA in the adipose tissue of obese and non­obese children was also assessed. Furthermore, the interaction between miR­424 and the adipocytokine TNF­α was determined. Finally, miR­424 target genes and downstream signaling pathways were predicted via bioinformatics and analyzed by performing a luciferase reporter assay to elucidate the functional mechanisms of miR­424 in adipogenesis of visceral adipocytes. The results revealed that the expression levels of miR­424 upregulated in the adipose tissue biopsies from obese children compared with the biopsies of non­obese children. However, in cultured adipocytes, the expression levels of miR­424 were discovered to be gradually downregulated during the adipogenesis process. TNF­α treatment significantly downregulated the expression levels of miR­424 via binding to its promoter region and reducing its transcriptional activity. Through bioinformatic prediction analysis, miR­424 target genes were analyzed, of which several were identified to be involved in signaling pathways that are known to regulate adipogenesis, such as the Wnt signaling pathway. In conclusion, the present study indicated that miR­424 was regulated by TNF­α and served an important role in adipogenesis.

Upregulation of long non-coding RNA MEG3 in type 2 diabetes mellitus complicated with vascular disease: a case-control study.

Previous studies have indicated that long non-coding RNAs (lncRNAs) were closely related to diabetes. In this study, we aimed to explore the possible role and mechanism of lncRNA MEG3 in the occurrence and development of type 2 diabetes mellitus (T2DM) and its vascular complications. A case-control study involving 115 subjects was conducted, including 53 T2DM patients (37 patients with vascular complication and 16 patients without vascular complications) and 62 healthy subjects. We performed real-time polymerase chain reaction (RT-PCR) analysis of the lncRNA MEG3 and miR-146a levels in peripheral blood mononuclear cells (PBMCs) in the 115 samples. We found that the expression of lncRNA MEG3 was upregulated in the T2DM patients with vascular complication (DC group) compared with T2DM patients without vascular complication (D group) (P < 0.05) and the control group (P < 0.01). miR-146a levels in DC group were significantly lower compared with control group. There was a significant positive correlation between the expression of lncRNA MEG3 and glucose (GLU) (r = 0.301, P = 0.0011) and hemoglobin A1C (HbA1c) (r = 0.477, P = 0.0006). Our study suggests MEG3 may play as an important role in progression of diabetes-related vascular complications, contributing to a novel understanding of pathogenesis and prognosis for diabetes and its complications.

Incorporation of Gene-Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients.

The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped for CYP3A4 20230T>C (rs2242480), CYP3A4 T>C (rs4646437), CYP3A5*3 6898A>G (rs776746), ABCB1 129T>C (rs3213619); ABCB1 c.1236C>T (rs01128503), ABCB1 c.2677G>T/A (rs2032582) and ABCB1 c.3435C>T (rs1045642) polymorphisms, and the effects of gene-gene and gene-environment interactions on the predictive accuracy of algorithm were evaluated. In wild-type CYP3A4 rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P < 1 × 10-4 ). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild-type CYP3A5 rs776746 carriers who had hypertension were higher than those without hypertension (P = 4.10 × 10-3 ). More importantly, dose-predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild-type CYP3A4 rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and CYP3A5 rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.

[A new phenolic compound from endophytic fungus Aspergillus fumigatus of Euphorbia royleana].

This research was carried out to study the secondary metabolites of endophytic fungus Aspergillosis fumigatus from Euphorbia royleana. The endophytic fungus A. fumigatus was fermented by solid fermentation,and purified by various chromatographic methods after extraction. The structures of the compounds were identified by1 H-NMR,13 C-NMR and HSQC,HMBC spectra and physicchemical properties. Three compounds were isolated and their structures were identified as 3-( 3,4-dihydroxybenzoyl)-5-( 3,4-dihydroxyphenyl)-6-methyl-5,6-dihydro-2 H-pyran-2-one( 1),hydroxysydonic acid( 2) and 11-hydroxysydonic acid( 3). Compound 1 is a new compound.

Tumour necrosis factor-related apoptosis-inducing ligand expression in patients with diabetic nephropathy.

OBJECTIVE: The objective of this study was to evaluate the expression profile of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in patients with diabetic nephropathy (DN). METHODS: A total of 126 Chinese subjects were enrolled in this study, including 42 patients with diabetes mellitus (DM), 42 patients with DN and 42 healthy controls. Real-time polymerase chain reaction was performed to analyze levels of TRAIL mRNA in peripheral blood mononuclear cells (PBMCs). Serum levels of soluble TRAIL (sTRAIL) and various cytokines were detected with a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Compared with the control group, the levels of TRAIL mRNA in PBMCs and sTRAIL in sera were both significantly decreased in the DM and DN patients ( P < 0.05). Conversely, levels of interleukin (IL)-1, IL-6, tumour necrosis factor-α and monocyte chemotactic protein-1 were higher in the DN group than in the control group. Serum levels of TRAIL positively correlated with TRAIL mRNA levels in all of the subjects examined ( P < 0.05). CONCLUSIONS: These results provide support and a theoretical basis for further research of TRAIL in regard to the pathogenesis of DN.

A systematic review of pharmacokinetic studies on herbal drug Fuzi: Implications for Fuzi as personalized medicine.

BACKGROUND: Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute toxicity. Aconitum alkaloids are responsible for its pharmacological activity and toxicity. Although a large number of studies on Fuzi have been reported, no comprehensive review on its pharmacokinetics has yet been published. PURPOSE: This paper seeks to present a comprehensive review regarding the phytochemistry, pharmacokinetic features and toxicity of Fuzi. The regulation of drug-metabolizing enzymes (DMEs) and efflux transporters (ETs) by Fuzi is also concluded. Additionally, the use of Fuzi as a personalized medicine based on the bioavailability barrier (BB), which mainly comprises DMEs and ETs, is discussed. METHODS: All available information on Fuzi was collected by searching for key words in PubMed, ScienceDirect, CNKI, Google Scholar, Baidu Scholar, and Web of Science. RESULTS: Aconitum alkaloids, which mainly include diester-diterpene alkaloids (DDAs), monoester-diterpene alkaloids (MDAs) and unesterified-diterpene alkaloids (UDAs), could be detected after Fuzi ingestion in vivo. The Aconitum alkaloids are rapidly absorbed in the intestine and extensively distributed in the body. DMEs, especially CYP3A4/5, are responsible for various types of metabolic reactions of the Aconitum alkaloids. ETs, including P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), are involved in the efflux of the DDAs and MDAs. The kidney is the most important organ involved in the excretion of the Aconitum alkaloids. DDAs are the main toxic compounds present in Fuzi, and their acute toxicity is mainly due to their effects on the voltage-dependent sodium channels. Furthermore, Fuzi can substantially regulate DMEs and ETs. CONCLUSIONS: The toxicity of DDAs is acute. However, further investigations are necessary to determine the exact toxicological mechanisms. The significant impact of Fuzi on DMEs and ETs suggests that the co-administration of Fuzi with drugs that are substrates of DMEs and/or ETs may cause herb-drug interactions (HDIs). The BB network controlled exposure to the Aconitum alkaloids in vivo. Polymorphisms of DMEs and ETs in different individuals contribute to the differences in the efficacy and toxicity of Fuzi ingestion. In the future, the use of Fuzi as personalized medicine based on the BB network is necessary and practical to achieve ideal therapeutic efficacy with minimal toxicity.

Corrigendum: Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients.

This corrects the article DOI: 10.1038/srep42192.

Nitric oxide as a signaling molecule in brassinosteroid-mediated virus resistance to Cucumber mosaic virus in Arabidopsis thaliana.

Brassinosteroids (BRs) are growth-promoting plant hormones that play a crucial role in biotic stress responses. Here, we found that BR treatment increased nitric oxide (NO) accumulation, and a significant reduction of virus accumulation in Arabidopsis thaliana. However, the plants pre-treated with NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxyl-3-oxide (PTIO)] or nitrate reductase (NR) inhibitor (tungstate) hardly had any NO generation and appeared to have the highest viral replication and suffer more damages. Furthermore, the antioxidant system and photosystem parameters were up-regulated in brassinolide (BL)-treated plants but down regulated in PTIO- or tungstate-treated plants, suggesting NO may be involved in BRs-induced virus resistance in Arabidopsis. Further evidence showed that NIA1 pathway was responsible for BR-induced NO accumulation in Arabidopsis. These results indicated that NO participated in the BRs-induced systemic resistance in Arabidopsis. As BL treatment could not increase NO levels in nia1 plants in comparison to nia2 plants. And nia1 mutant exhibited decreased virus resistance relative to Col-0 or nia2 plants after BL treatment. Taken together, our study addressed that NIA1-mediated NO biosynthesis is involved in BRs-mediated virus resistance in A. thaliana.

Aconitum alkaloids, the major components of Aconitum species, affect expression of multidrug resistance-associated protein 2 and breast cancer resistance protein by activating the Nrf2-mediated signalling pathway.

BACKGROUND: Aconitum alkaloids from Aconitum species are often used to treat arthritis and rheumatic diseases but have the drawback of high toxicity. Identifying their pharmacokinetic behaviour is important for the safe clinical application of Aconitum species. Efflux transporters (ETs), including P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), have important functions in regulating the pharmacokinetic behaviours of drugs and in herb-herb or herb-drug interactions (HDIs). The Aconitum alkaloids regulate P-gp expression and function, but their effects on MRP2 and BCRP expression remain unknown. PURPOSE: To determine the effects of three Aconitum alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, on MRP2 and BCRP. METHODS: The levels of the protein and mRNA expression of MRP2 and BCRP in vivo and in vitro were measured via Western blotting and real-time PCR, respectively. Fluorescence signals of MRP2 and BCRP were detected via confocal fluorescence microscopy. A reporter assay using HepG2-C8 cells, which were generated by transfecting plasmids containing the antioxidant response element (ARE)-luciferin gene into HepG2 cells, was used to examine the ARE-luciferin activity. The transport activities of MRP2 and BCRP were tested via flow cytometry using substrate probes. RESULTS: The Aconitum alkaloids significantly up-regulated MRP2 and BCRP expression, accompanied by a marked increase in nuclear factor E2-related factor-2 (Nrf2) expression in the jejunum, ileum, and colon of FVB mice, in the order AC < BAC < aconine. In the in vitro model, the Aconitum alkaloids increased MRP2 and BCRP expression in Caco-2 and LS174T cells, in the order AC < BAC < aconine. Additionally, these alkaloids promoted the translocation of Nrf2 from the cytoplasm to the nucleus and significantly increased ARE-luciferin activity in HepG2-C8 cells. Luteolin, a potent inhibitor of Nrf2, markedly prevented MRP2 and BCRP expression from being induced by the three Aconitum alkaloids. The efflux activity of MRP2 was also significantly increased in cells receiving the same treatment. CONCLUSIONS: The tested Aconitum alkaloids significantly increased the expression of MRP2 and BCRP by activating the Nrf2-mediated signalling pathway and enhanced the efflux activity of MRP2. The potential for herb-herb interactions or HDIs exists when Aconitum species are co-administered with substrate drugs that are transported via MRP2 and BCRP. Therefore, the Aconitum alkaloids may be used as quality indicators for the herbs of Aconitum species.

LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine.

This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and RT-PCR were used along with SULT activity measurement using probe substrates. The LC-MS/MS method was specific for all five tested SULTs, whereas Western blot was specific for only two isoforms. The activities of SULT1A1, SULT1B1, SULT1E1 and SULT2A1 in 9 of 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tissues, whereas the activities of SULT1A3 in 7 of 10 samples increased. The turnover numbers of SULTs did not change, except for SULT1A1. A generally high degree of correlations was observed between SULT activities and protein amounts (r2 ≥ 0.59 except one), whereas a low degree of correlations was observed between SULT activities and mRNA expression levels (r2 ≤ 0.48 except one). HCC reduced the SULT activities via impaired protein amounts. LC-MS/MS quantification of SULTs is highly reliable measurement of SULT activities, and may be adopted for implementing precision medicine with respect to drugs mainly metabolized by SULTs in healthy and HCC patients.

Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients.

Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the "derivation cohort" to develop dose-prediction algorithm, while the remaining 20% constituted the "validation cohort" to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.