Causal role of immune cells in major depressive disorder and bipolar disorder: Mendelian randomization (MR) study.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are prevalent psychiatric conditions linked to inflammatory processes. However, it is unclear whether associations of immune cells with these disorders are likely to be causal. METHODS: We used two-sample Mendelian randomization (MR) approach to investigate the relationship between 731 immune cells and the risk of MDD and BD. Rigorous sensitivity analyses are conducted to assess the reliability, heterogeneity, and horizontal pleiotropy of the findings. RESULTS: Genetically-predicted CD27 on IgD+ CD38- unswitched memory B cell (inverse variance weighting (IVW): odds ratio (OR) [95 %]: 1.017 [1.007 to 1.027], p = 0.001), CD27 on IgD+ CD24+ B cell (IVW: OR [95 %]: 1.021 [1.011 to 1.031], p = 4.821E-05) and other 12 immune cells were associated with increased risk of MDD in MR, while HLA DR++ monocyte %leukocyte (IVW: OR [95 %]: 0.973 [0.948 to 0.998], p = 0.038), CD4 on Central Memory CD4+ T cell (IVW: OR [95 %]: 0.979 [0.963 to 0.995], p = 0.011) and other 13 immune cells were associated with decreased risk of MDD in MR. Additionally, CD33+ HLA DR+ Absolute Count (IVW: OR [95 %]: 1.022[1.007 to 1.036], p = 0.007), CD28+ CD45RA- CD8+ T cell %T cell (IVW: OR [95 %]: 1.024 [1.008 to 1.041], p = 0.004) and other 18 immune cells were associated with increased risk of BD in MR, while CD62L on CD62L+ myeloid Dendritic Cell (IVW: OR [95 %]: 0.926 [0.871 to 0.985], p = 0.014), IgD- CD27- B cell %lymphocyte (IVW: OR [95 %]: 0.918 [0.880 to 0.956], p = 4.654E-05) and other 13 immune cells were associated with decreased risk of BD in MR. CONCLUSIONS: This MR study provides robust evidence supporting a causal relationship between immune cells and the susceptibility to MDD and BD, offering valuable insights for future clinical investigations. Experimental studies are also required to further examine causality, mechanisms, and treatment potential for these immune cells for MDD and BD.

Structural biology of terpene synthases.

Structural biology research of terpene synthases (TSs) has provided a useful basis to understand their catalytic mechanisms in producing diverse terpene products with polycyclic ring systems and multiple chiral centers. However, compared to the large numbers of>95,000 terpenoids discovered to date, few structures of TSs have been solved and the understanding of their catalytic mechanisms is lagging. We here (i) introduce the basic catalytic logic, the structural architectures, and the metal-binding conserved motifs of TSs; (ii) provide detailed experimental procedures, in gene cloning and plasmid construction, protein purification, crystallization, X-ray diffraction data collection and structural elucidation, for structural biology research of TSs; and (iii) discuss the prospects of structure-based engineering and de novo design of TSs in generating valuable terpene molecules, which cannot be easily achieved by chemical synthesis.

[Elucidating the Impacts of Meteorology and Emission Changes on Concentrations of Major Air Pollutants in Major Cities in the Yangtze River Delta Region Using a Machine Learning De-weather Method].

This study applied a de-weather method based on a machine learning technique to quantify the contribution of meteorology and emission changes to air quality from 2015 to 2021 in four cities in the Yangtze River Delta Region. The results showed that the significant reductions in PM2.5, NO2, and SO2 emissions(57.2%-68.2%, 80.7%-94.6%, and 81.6%-96.1%, respectively) offset the adverse effects of meteorological conditions, resulting in lower pollutant concentrations. The meteorological contribution of maximum daily 8-h average O3(MDA8_O3) showed a stronger effect than that of others(23.5%-42.1%), and meteorological factors promoted the increase in MDA8_O3 concentrations(4.7%); however, emission changes overall resulted in a decrease in MDA8_O3 concentrations(-3.2%). NO2 and MDA8_O3 decreased more rapidly from 2019 to 2021, mainly because the emissions played a stronger role in reducing pollutant concentrations than from 2015 to 2018. However, emissions changes had weaker reduction effects on PM2.5 and SO2 from 2019 to 2021 than from 2015 to 2018. De-weather methods could effectively seperate the effects of meteorology and emission changes on pollutant trends, which helps to evaluate the real effects of emission control policies on pollutant concentrations.

Lifestyle interventions to prevent adverse pregnancy outcomes in women at high risk for gestational diabetes mellitus: a randomized controlled trial.

Objective: To examine the effects of lifestyle interventions, including dietary guidance, health education and weight management, on pregnancy outcomes in women at high risk of gestational diabetes mellitus (GDM). Methods: Our study included 251 women at high risk of GDM and 128 randomized to lifestyle interventions (dietary guidance, health education, and weight management); One hundred and twenty-three people were randomly assigned to a control group (regular pregnancy check-ups). Counts between groups were compared using either chi-square test or Fisher's exact test. Results: Compared with the control group, the risk of GDM was reduced by 46.9% (16.4% vs 30.9%, P = 0.007) and the risk of pregnancy induced hypertension (PIH) was reduced by 74.2% (2.3% vs 8.9%, P = 0.034) in the intervention group. There were no significant differences in macrosomia, cesarean section, or preterm birth (P >0.05). Conclusion: The lifestyle intervention in this study helped pregnant women to better understand knowledge related to pregnancy, reduce stress and anxiety, and increase intake of adequate prenatal nutrition. This intervention prevented metabolic abnormalities that may occur due to inadequate nutrient intake during pregnancy. In addition, it helped women to control weight gain, maintain appropriate weight gain during pregnancy, and reduce the risk of excessive or insufficient weight gain, ultimately lowering the incidence of GDM and PIH. This highlights the importance of early screening and intervention for high-risk pregnant women. Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2300073766.

Developing and validating a nomogram for cognitive impairment in the older people based on the NHANES.

Objective: To use the United States National Health and Nutrition Examination Study (NHANES) to develop and validate a risk-prediction nomogram for cognitive impairment in people aged over 60 years. Methods: A total of 2,802 participants (aged ≥ 60 years) from NHANES were analyzed. The least absolute shrinkage and selection operator (LASSO) regression model and multivariable logistic regression analysis were used for variable selection and model development. ROC-AUC, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram's performance. Results: The nomogram included five predictors, namely sex, moderate activity, taste problem, age, and education. It demonstrated satisfying discrimination with a AUC of 0.744 (95% confidence interval, 0.696-0.791). The nomogram was well-calibrated according to the calibration curve. The DCA demonstrated that the nomogram was clinically useful. Conclusion: The risk-prediction nomogram for cognitive impairment in people aged over 60 years was effective. All predictors included in this nomogram can be easily accessed from its' user.

Development and validation of mathematical nomogram for predicting the risk of poor sleep quality among medical students.

Background: Despite the increasing prevalence of poor sleep quality among medical students, only few studies have identified the factors associated with it sing methods from epidemiological surveys. Predicting poor sleep quality is critical for ensuring medical Students' good physical and mental health. The aim of this study was to develop a comprehensive visual predictive nomogram for predicting the risk of poor sleep quality in medical students. Methods: We investigated medical Students' association with poor sleep quality at JiTang College of North China University of Science and Technology through a cross-sectional study. A total of 5,140 medical students were randomized into a training cohort (75%) and a validation cohort (25%). Univariate and multivariate logistic regression models were used to explore the factors associated with poor sleep quality. A nomogram was constructed to predict the individual risk of poor sleep quality among the medical students studied. Results: 31.9% of medical students in the study reported poor sleep quality. We performed multivariate logistic analysis and obtained the final model, which confirmed the risk and protective factors of poor sleep quality (p < 0.05). Protective factors included the absence of physical discomfort (OR = 0.638, 95% CI: 0.546-0.745). Risk factors included current drinking (OR = 0.638, 95% CI: 0.546∼0.745), heavy study stress (OR = 2.753, 95% CI: 1.456∼5.631), very heavy study stress (OR = 3.182, 95% CI: 1.606∼6.760), depressive symptoms (OR = 4.305, 95% CI: 3.581∼5.180), and anxiety symptoms (OR = 1.808, 95% CI: 1.497∼2.183). The area under the ROC curve for the training set is 0.776 and the area under the ROC curve for the validation set is 0.770, which indicates that our model has good stability and prediction accuracy. Decision curve analysis and calibration curves demonstrate the clinical usefulness of the predictive nomograms. Conclusion: Our nomogram helps predict the risk of poor sleep quality among medical students. The nomogram used includes the five factors of drinking, study stress, recent physical discomfort, depressive symptoms, and anxiety symptoms. The model has good performance and can be used for further research on and the management of the sleep quality of medical students.

The full-length genome sequence of a novel amalgavirus in Lilium spp. in China.

We report for the first time the complete genome sequence of a novel amalgavirus, tentatively designated as 'lily amalgavirus 1' (LAV-1), isolated from Lilium spp. in China. LAV-1 is a 3448-nt double-stranded RNA virus that encodes two putative proteins. Open reading frame 1 (ORF1) encodes a 394-aa protein with unknown function. ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp) of 895 aa. The two ORFs putatively encode a '1 + 2' fusion protein generated by a '+1' programmed ribosomal frameshift (PRF). BLASTp analysis revealed that the complete genome sequence of LAV-1 shares 48.23-59.80% sequence identity (query sequence coverage > 77%) with those of members of the genus Amalgavirus, with the highest nucleotide sequence identity of 59.80% with that of Allium cepa amalgavirus 1 (query sequence coverage, 87%). The genome structure, phylogenetic relationships, and sequence similarities to other plant amalgaviruses suggest that LAV-1 is a new member of the genus Amalgavirus.

Stereoselective gold(I)-catalyzed approach to the synthesis of complex α-glycosyl phosphosaccharides.

Glycosyl phosphosaccharides represent a large and important family of complex glycans. Due to the distinct nature of these complex molecules, efficient approaches to access glycosyl phosphosaccharides are still in great demand. Here, we disclose a highly efficient and stereoselective approach to the synthesis of biologically important and complex α-glycosyl phosphosaccharides, employing direct gold(I)-catalyzed glycosylation of the weakly nucleophilic phosphoric acid acceptors. In this work, the broad substrate scope is demonstrated with more than 45 examples, including glucose, xylose, glucuronate, galactose, mannose, rhamnose, fucose, 2-N3-2-deoxymannose, 2-N3-2-deoxyglucose, 2-N3-2-deoxygalactose and unnatural carbohydrates. Here, we show the glycosyl phosphotriester prepared herein was successfully applied to the one-pot synthesis of a phosphosaccharide from Leishmania donovani, and an effective preparation of a trisaccharide diphosphate of phosphosaccharide fragments from Hansenula capsulate via iterative elongation strategy is realized.

Design, synthesis, and biological evaluation of 1-substituted -2-aryl imidazoles targeting tubulin polymerization as potential anticancer agents.

A series of novel 1-substituted-2-aryl imidazoles (SAI) were designed and synthesized based on our previously reported ABI (2-Aryl-4-Benzoyl Imidazole) analogs and on the structure of combretastatin A-4 (CA-4). These compounds showed potent antiproliferative activities against six human cancer cell lines with IC50 values in nano molar range. Among them, compound 3X exhibited the best anticancer activity with an average IC50 value of ∼100 nM. The compound maintains the mechanism of action by inhibiting tubulin polymerization, thus causing cell arrest at G2/M phase and apoptosis. In vivo efficacy studies indicated that 3X was highly effective in suppressing tumor growth in a MDA-MB-468 xenograft model of nude mouse with a TGI (Tumor Growth Suppression) of 77% at 60 mg/kg without causing significant toxicity. In addition, 3X displayed significantly better water solubility (36.70 µg/mL) than CA-4 (2.83 µg/mL). Molecular modeling study indicated that 3X binds well to the colchicine binding site in tubulin. Our results suggest that the novel SAI analogs deserve further investigation as potential anticancer agents.