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Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine‐tuned rigid three‐dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C−C and C−O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post‐translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450‐modified multicyclic RiPPs, we set out to find cryptic and unknown P450‐modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450‐modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450‐modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450‐modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring‐forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane‐containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives. [ABSTRACT FROM AUTHOR]

Background and Objective: Inflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers and the development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase‐9 (MMP‐9), Tissue inhibitor metalloproteinase‐1 (TIMP‐1), Monocyte Chemoattractant Protein‐1 (MCP‐1) are several inflammatory biomarkers that are potentially involved in the development of CSVD. In this present study, we aimed to investigate the relationship between candidate molecules and CSVD features. Method: The concentration of each biomarker was measured in 79 acute ischemic stroke patients admitted within 72 h after symptom onset. The associations between blood levels of inflammatory markers and CSVD score were investigated, as well as each CSVD feature, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS). Results: The mean age was 69.0 ± 11.8 years, and 65.8% of participants were male. Higher SERPINA3 level (>78.90 ng/mL) was significantly associated with larger WMH volume and higher scores on Fazekas's scale in all three models. Multiple regression analyses revealed the linear association between absolute WMH burden and SERPINA3 level, especially in model 3 (β = 0.14; 95% confidence interval [CI], 0.04–0.24;p =0.008). Restricted cubic spline regression demonstrated a dose–response relationship between SERPINA3 level and larger WMH volume (p nonlineariy = 0.0366 and 0.0378 in model 2 and mode 3, respectively). Using a receiving operating characteristic (ROC) curve, plasma SERPINA3 level of 64.15 ng/mL distinguished WMH >7.8 mL with the highest sensitivity and specificity (75.92% and 60%, respectively, area under curve [AUC] = 0.668, p = 0.0102). No statistically significant relationship has been found between other candidate biomarkers and CSVD features. Conclusion: In summary, among four inflammatory biomarkers that we investigated, SERPINA3 level at baseline was associated with WMH severity, which revealed a novel biomarker for CSVD and validated its relationship with inflammation and endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short‐term recovery trajectories among ICH patients with early cognitive impairment. Methods: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini‐mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. Results: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1‐year increase, 1.037; 95% confidence interval [CI], 1.003–1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1‐point increase, 1.146; 95% CI, 1.065–1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810–12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133–0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503–12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). Interpretation: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short‐term functional recovery. [ABSTRACT FROM AUTHOR]

[Objectives] This study aims to ascertain the effects of temperature on the growth and development of Atractomorpha sinensis, as well as the response of adult antioxidant enzymes to different temperatures. [Methods] The developmental duration, survival rate, fecundity and population growth index of various larval age stages raised on soybeans, and adult antioxidant enzyme activity, were measured and compared at temperatures of 16, 20, 24, 28 and 32 °C. [Results] The duration of larval development and adult pre-oviposition (oviposition) were shorter at higher temperatures. The survival rate of the nymph stage was highest (68.97%) at 24 °C. The developmental threshold temperature and effective accumulated temperature of a complete generation were 10.77 °C and 1 481.52 degree-days, respectively. The population net reproduction rate (R0) and population trend index (I) were highest (75.33 and 21.22, respectively) at 24 °C, lowest (33.67 and 9.25, respectively) at 16 °C, and intermediate (41.75 and 12.51 respectively, at 28 °C. Adults have a free radical-scavenging, antioxidant enzyme system and adult longevity and population life table parameters are significantly, and positively, correlated with antioxidant enzyme activity. [Conclusion] The results suggest that 24 °C was the optimum temperature for the reproduction of A. sinensis and that there is a close relationship between ambient temperature and antioxidant enzyme activity. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH). Methods: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4–6 at 3 months. Results: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26–8.48, p = 0.015). Conclusion: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH. [ABSTRACT FROM AUTHOR]

Given the importance of crude oil prices in the world economy, accurate price prediction has drawn extensive attention. Nevertheless, because of the complexity of the crude oil market, most traditional forecasting algorithms fail to meet the accuracy requirements. To achieve higher precision, this paper proposes a novel hybrid model for crude oil price forecasting by combining a Hodrick-Prescott filter with X12 methods and adjusting the order used. Application of our model on both West Texas Intermediate and Brent oil prices forecasting demonstrates its accuracy. The results of various forecasting performance evaluation criteria indicate that the model has stronger stability and better accuracy. The mechanism of seasonal and periodic factors is also analyzed, which provides remarkable references to other time-series predictions. Establishing two different types of predictive models that combine multiple knowledge effectively has obvious advantages over other models and provides more reliable cutting-edge information for designing a Chinese energy development strategy. [ABSTRACT FROM AUTHOR]