Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis.

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

Osteoarthritis and hypertension: observational and Mendelian randomization analyses.

BACKGROUND: The association between osteoarthritis (OA) and hypertension is a subject of ongoing debate in observational research, and the underlying causal relationship between them remains elusive. METHODS: This study retrospectively included 24,871 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2020. Weighted logistic regression was performed to investigate the connection between OA and hypertension. Additionally, Mendelian randomization (MR) analysis was conducted to explore the potential causal relationship between OA and hypertension. RESULTS: In the NHANES data, after adjusting for multiple confounding factors, there was no significant relationship between OA and hypertension (OR 1.30, 95% CI, 0.97-1.73, P = 0.089). However, among males, OA appeared to be associated with a higher risk of hypertension (OR 2.25, 95% CI, 1.17-4.32, P = 0.019). Furthermore, MR results indicate no relationship between multiple OA phenotypes and hypertension: knee OA (IVW, OR 1.024, 95% CI: 0.931-1.126, P = 0.626), hip OA (IVW, OR 0.990, 95% CI: 0.941-1.042, P = 0.704), knee or hip OA (IVW, OR 1.005, 95% CI: 0.915-1.105, P = 0.911), and OA from UK Biobank (IVW, OR 0.796, 95% CI: 0.233-2.714, P = 0.715). Importantly, these findings remained consistent across different genders and in reverse MR. CONCLUSIONS: Our study found that OA patients had a higher risk of hypertension only among males in the observational study. However, MR analysis did not uncover any causal relationship between OA and hypertension.

[Seasonal dynamics in photosynthetic characteristics and growth of Cunninghamia lanceolata saplings and their response to soil warming]. / æ‰æœ¨å¹¼æ ‘å ‰åˆç‰¹æ€§ä¸Žç”Ÿé•¿çš„å­£èŠ‚å˜åŒ–åŠå ¶å¯¹åœŸå£¤å¢žæ¸©çš„å“åº”.

In order to understand the response and adaptation mechanisms of photosynthetic characteristics and growth for Cunninghamia lanceolata saplings in the subtropical region to global warming, we conducted the root-box warming experiment (ambient, ambient+4 ℃) at the Sanming Forest Ecosystem National Observation and Research Station in Fujian Province to investigate the effects of soil warming on the photosynthetic characteristics and growth of C. lanceolata saplings in different seasons. The results showed that the net photosynthetic rate (Pn) and stomatal conductance (gs) of C. lanceolata significantly decreased in summer compared with in spring and autumn. Soil warming had no effect on the Pn and gs of C. lanceolata. However, the interaction between warming and season significantly impacted the leaf water use efficiency (WUE). The tree height and ground diameter growth of C. lanceolata significantly increased in spring compared with in summer and autumn. Warming significantly reduced ground diameter growth, and it diminished the net diameter growth by 48.1% in autumn. However, warming had no impact on the tree height growth of C. lanceolata in each season. The specific leaf area, soluble sugar, and non-structural carbohydrates contents of C. lanceolata significantly improved in summer and autumn compared with in spring. Warming had rarely influence on leaf functional traits in each season. In conclusion, the response of photosynthesis for C. lanceolata to soil warming was insignificant. The photosynthesis of C. lanceolata exhibited significant seasonal dynamics, primarily controlled by gs. C. lanceolata adapted to soil warming by adjusting WUE, and it adjusted to high temperatures and drought stress in summer by increasing soluble sugar content and specific leaf area. The effect of warming on ground diameter growth of C. lanceolata was primarily driven by soil moisture. The seasonal difference in the growth of C. lanceolata was influenced by the photosynthesis of C. lanceolata and the trade-off between the utilization and storage of photosynthetic products.

Causal Relationship Between Immune Cells/Cytokines and Dilated Cardiomyopathy.

To date, whether there is any causal relationship between dilated cardiomyopathy (DCM) and the changes in the levels/expression of immune cells/cytokines is still unclear. This study aimed to investigate the causal relationship between the levels of various types of immune cells/cytokines and DCM. Herein, two-sample Mendelian randomization (MR) (TSMR) using R software was conducted. Single nucleotide polymorphisms (SNPs) related to the levels of various types of immune cells/cytokines and DCM were screened based on the genome-wide association studies (GWAS) obtained from open-source databases. The TSMR was conducted using inverse variance weighted (IVW), method, MR-Egger regression, weighted median method, and simple estimator based on mode to explore the causal association between the levels of each immune cell/cytokine and DCM. Sensitivity analysis was conducted using MR-Egger regression and a leave-one-out sensitivity test. A total of 1816 SNPs related to host immune status and DCM were identified. The IVW results showed a relationship between DCM and the circulating levels of basophils/eosinophils, total eosinophils-basophils, lymphocytes, and C-reactive protein (CRP). Increased lymphocytes levels (odds ratio (OR) = 0.91, 95% confidence interval (CI): 0.84-0.97, P = 0.005) were seen as protective against DCM, whereas increased basophil (OR = 1.18, 95% CI: 1.04-1.33, P = 0.022), eosinophil (OR = 1.1, 95% CI: 1.03-1.17, P = 0.007), eosinophil-basophil (OR = 1.09, 95% CI: 1.02-1.17, P = 0.014), and CRP (OR = 1.1, 95% CI: 1.03-1.18, P = 0.013) levels were associated with an increased risk of DCM. These analyses revealed that there may be a relationship between immune cells/select cytokine status and the onset of DCM. Future studies are required to further validate these outcomes in animal models and clinical trials.

Associations of body roundness index with cardiovascular and all-cause mortality: NHANES 2001-2018.

Body roundness index (BRI) was associated with cardiovascular diseases. But the relationship between BRI with cardiovascular disease (CVD) mortality and all-cause mortality remains largely unknown in hypertensive patients. This prospective cohort study included patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2018, and aimed to evaluate the association between BRI with CVD mortality and all-cause mortality. A total of 15570 patients were included. Over a median follow-up of 8.0 years (interquartile range, 4.3-12.6 years), 3445 individuals died, including 1166 CVD deaths. Weighted restricted cubic spline regression results showed a nonlinear association between BRI and CVD mortality and all-cause mortality (both P for nonlinear trend <0.001). The weighted multivariate Cox proportional hazards regression showed the hazard ratio (HRs) for CVD mortality were 0.93 (95% CI: 0.84-1.03, P = 0.160) in the low levels of BRI (≤5.9) and 1.11 (95% CI: 1.05-1.19, P < 0.001) in the high levels of BRI (>5.9). Similar associations were observed for all-cause mortality, the HRs were 0.91 (95% CI: 0.87-0.96, P < 0.001) in the low levels of BRI (≤6.3) and 1.09 (95% CI: 1.05-1.13, P < 0.001) in the high levels of BRI (>6.3). This cohort study supported that BRI was nonlinearly associated with CVD mortality and all-cause mortality among patients with hypertension. The thresholds of 5.9 and 6.3 for CVD mortality and all-cause mortality, respectively, may represent intervention targets for lowering the risk of premature death, but this needs to be confirmed in large clinical trials.

Exploring the diagnostic and prognostic value of the C-reactive protein/lymphocyte ratio for dilated cardiomyopathy based on a real-world study.

To determine the risk factors for dilated cardiomyopathy (DCM) and construct a risk model for predicting HF in patients with DCM, We enrolled a total of 2122 patients, excluding those who did not meet the requirements. A total of 913 patients were included in the analysis (611 males and 302 females) from October 2012 to May 2020, and data on demographic characteristics, blood biochemical markers, and cardiac ultrasound results were collected. Patients were strictly screened for DCM based on the diagnostic criteria. First, these patients were evaluated using propensity score matching (PSM). Next, unconditional logistic regression was used to assess HF risk. Furthermore, receiver operating characteristic (ROC) curve analysis was conducted to determine diagnostic efficiency, and a nomogram was developed to predict HF. Finally, the Kaplan‒Meier survival curve was plotted. Of the initial 2122 patients, the ejection fraction (EF) in males was worse. We included 913 patients after the final DCM diagnosis. The results showed that the levels of NT-proBNP, WBC, PLT, neutrophils, lymphocytes, eosinophils, and IL-6, C-reactive protein (CRP) and the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CRP/lymphocyte ratio (CLR) were higher in males than in females (P < 0.001-0.009). The nomogram showed that factors such as sex, WBC, neutrophils, PLR, and CLR could predict the risk of worsening cardiac function in patients with DCM before and after PSM (P < 0.05). The ROC curve showed that CLR with an 85.6% area demonstrated higher diagnostic efficacy than the NLR (77.0%) and PLR (76.6%, P < 0.05). Survival analysis showed a higher mortality risk in females with higher CLR levels (P < 0.001-0.009). However, high CLR levels indicated a higher mortality risk (P < 0.001) compared to sex. Male EF is lower in DCM patients. CLR could predict the risk of declined cardiac function in patients with DCM. The mortality in females with higher CLR levels was highest; however, the exact mechanism should be investigated.

[Research for the influencing factors affecting the long-term survival time of implants: a retrospective cohort study].

PURPOSE: To investigate the timing of implant failure events and their relationship with the dental position and the factors affecting the survival time of implants. METHODS: A retrospective cohort study was conducted to analyze the patients who had implants removed due to implant failure in the Department of Dental Implantology of Hefei Stomatological Hospital from January 2019 to December 2021. The predictor variables were surgical age, gender, smoking habit, oral hygiene, glucose value, jaw and dental position, implant type, implant number, surgeon, implant placement timing, implant loading timing, and antibiotic use timing. The outcome measurement was the implant survival time and implant failure events. Chi-square test, Kaplan-Meier(Log-rank test), and Cox proportional hazards model were used to identify and stepwise determined potential risk factors for implant survival time with SPSS 21.0 software package. RESULTS: A total of 89 patients(95 implants) had to remove implants. The mean survival time of the failed implants was 31(95%CI :24.2-39.1) months. Implant number (P=0.038), implant loading timing (P=0.050), and tooth position (P=0.024) were significantly correlated with the implant survival time. The risk of failure with 2 implants was 2.709 (HR=3.709, 95%CI: 1.075-12.795) times higher than that with 1 implant, and the risk of failure with late implant loading was 0.551(HR=1.511, 95%CI: 0.999-2.406) times higher than that with early implant loading. The risk of anterior teeth implant failure was 1.384 times higher than that of molars(HR=2.384, 95%CI:1.327-4.283). For patients with implant failure, about 50% of the patients removed the failed implant within 1 year after surgery, and the rate of removal of the failed implant gradually slowed down in the following 2-10 years. Peri-implantitis most commonly occurred in molars(50%). Implant fracture lastly occurred at 55(95%CI: 42.2-67.9) months postoperatively（P=0.000）. CONCLUSIONS: The number of implants, implant loading timing, and dental position were considered as the influencing factors for the survival time of implants. Follow-up in the first year after implantation seems to be particularly important for timely detection of problems and timely intervention. The occurrence of implant failure events was related to dental position and time.

Searching for Intrinsic Causality between Colonic Dysbiosis and Non-Ischemic Cardiomyopathy: A Mendelian Randomization-Based Analysis.

Objective: Little is known about gut microbiota (GM) and cardiomyopathy. Their causal relationship was explored using two-sample Mendelian randomization (TSMR) performed by R software. Methods: The single nucleotide polymorphisms (SNPs) were further screened based on the genome-wide association studies (GWAS) of gut microbiota and cardiomyopathy obtained from an open database. TSMR was performed using an MR-Egger regression, simple estimator based on mode, weighted median method, inverse variance weighted (IVW), weighted estimator and CML-MA-BIC to explore the causal association. And the sensitivity analysis was carried out using an MR-Egger regression and the leave-one-out sensitivity test. Results: As for 211 GM taxa, IVW results confirmed that the class Actinobacteria (OR = 0.81, p = 0.021) and genus Coprobacter (OR = 0.85, p = 0.033) were protective factors for cardiomyopathy. The phylum Firmicutes (OR = 0.87, p < 0.01), family Acidaminococcaceae (OR = 0.89, p < 0.01), genus Desulfovibrio (OR = 0.92, p = 0.030) and genus Prevotella9 (OR = 0.93, p = 0.029) were protective factors for ischemic cardiomyopathy. The family Rhodospirillaceae (OR = 1.06, p = 0.036) and genus Turicibacter (OR = 1.09, p = 0.019) were risk factors for ischemic cardiomyopathy. The genus Olsenella (OR = 0.91, p = 0.032) was a protective factor for non-ischemic cardiomyopathy. The order Rhodospirillales (OR = 1.14, p = 0.024), family Rikenellaceae (OR = 1.21, p = 0.012) and genus Gordonibacter (OR = 1.12, p = 0.019) were risk factors for non-ischemic cardiomyopathy. The robustness of MR results was reflected in the heterogeneity (p > 0.05) and pleiotropy (p > 0.05) analyses. Conclusions: A potential causal relationship of cardiomyopathy with some GM taxa has been confirmed in the current study.

Mechanism of salidroside against coronary artery disease by network pharmacology analysis.

BACKGROUND: Rosenroot (Rhodiola rosea) is a traditional Chinese herbal medicine. It has been used to treat patients with coronary artery disease (CAD). Salidroside is the main active constituent of rosenroot. This study was designed to explore the mechanism of salidroside in treating CAD and its role in angiogenesis in CAD systematically. METHODS: In this study, potential targets related to salidroside and CAD were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and CellMarker enrichment analyses were performed. The binding of salidroside to angiogenesis-related targets was assessed by PyMOL and Ligplot. Furthermore, the effects of salidroside on collateral circulation were evaluated by correlation analysis of these angiogenesis-related targets with the coronary flow index (CFI), and the influence of salidroside on human umbilical vein endothelial cell (HUVEC) proliferation and migration was assessed. RESULTS: Eighty-three targets intersected between targets of salidroside and CAD. GO and KEGG analyses indicated that salidroside mainly treated CAD through angiogenesis and anti-inflammatory action. There were 12 angiogenesis-related targets of salidroside in coronary heart disease, among which FGF1 (r = 0.237, P = 2.597E-3), KDR (r = 0.172, P = 3.007E-2) and HIF1A (r = -0.211, P = 7.437E-3) were correlated with the coronary flow index (CFI), and salidroside docked well with them. Finally, cell experiments confirmed that salidroside promoted the proliferation and migration of HUVECs. CONCLUSIONS: This study revealed the potential molecular mechanism of salidroside on angiogenesis in CAD and provided new ideas for the clinical application of salidroside in the treatment of CAD.

Effects of warming on quantity and structure of litter-derived dissolved organic matter in subtropical natural Castanopsis kawakamii forests.

Litter-derived dissolved organic matter (DOM) is an important source of soil DOM, and the response of which to climate warming may change forest soil carbon and nitrogen dynamics, such as soil carbon and nitrogen mineralization. In this study, we conducted a field manipulative warming experiment in natural Castanopsis kawakamii forests. Combined with litter leaching solution collected in the field and ultraviolet-visible and three-dimensional fluorescence spectroscopy analyses, we explored the effects of warming on the content and structure of litter-derived DOM in subtropical evergreen broad-leaved forests. The results showed that litter-derived dissolved organic carbon and nitrogen content exhibited monthly dynamics, with the peak (in April) and the mean monthly content being 1.02 and 0.15 g·m-2, respectively. Litter-derived DOM had higher fluorescence index and lower biological index, indicating the microbial-origin of DOM from litter. The litter DOM mainly included humic-like fractions and tryptophan-like substances. Warming did not affect the content, aromaticity, hydrophobicity, molecular weight, fluorescence index, biological index and humification index of DOM, suggesting neutral effect of warming on the quantity and structure of litter DOM. Warming also did not affect the relative contribution of main components in DOM, indicating that the temperature variation exerted no effects on microbial degradation. In summary, warming did not change the quantity and quality of litter-derived DOM in subtropical evergreen broadleaved forests, indicating warming had little effect on litter-derived DOM input to soil.

Soil warming decreased dissolved organic carbon quantity and quality in subtropical forests.

Soil dissolved organic carbon (DOC) is the most active part in forest soil carbon pool, the responses of which to climate warming has profound effects on forest carbon cycling. Based on a manipulative soil warming experiment in subtropical evergreen broad-leaved forests, we collected soil solutions in situ and used ultraviolet-visible, infrared and three-dimensional fluorescence spectroscopy analyses to explore the effects of soil warming (+4 ℃, 1 year) on soil DOC quantity and quality along the soil profile. The results showed that soil DOC flux remained constant along the soil profile. Soil DOC mainly included two humic-like fractions and one microbial metabolite. Warming significantly decreased soil DOC flux and the abundance of aromatic and hydrophobic components, and increased the amount of low molecular weight carbohydrates. Furthermore, soil warming increased the relative proportion of humic-like fractions in the surface soil layer (0-10 cm) and microbial metabolite in the deep soil layer (30-40 cm), indicating that warming might accelerate microbial turnover in the deep layer. Overall, soil warming not only decreased soil DOC content, but also simplified the composition of soil DOC in subtropical evergreen broad-leaved forests.

[Effects of management on the content and spectral characteristics of soil dissolved organic carbon in a subtropical forest]. / ç»è¥æ–¹å¼å¯¹äºšçƒ­å¸¦æ£®æž—åœŸå£¤å¯æº¶æ€§æœ‰æœºç¢³å«é‡å’Œå ‰è°±å­¦ç‰¹å¾çš„å½±å“.

The differences of artificial measures, such as logging residue management, between assisted natural regeneration and afforestation may change the content and structure of soil dissolved organic carbon (DOC) and affect forest carbon cycle. In this study, we investigated the effects of managements on the content and spectral characteristics of DOC in a subtropical forest, which contained the forest of assisted natural regeneration (Ⅱ), and the plantation (Ⅲ), both were converted from mature secondary forests (Ⅰ). Results showed that DOC content in the 0-10 cm soil layer was significantly decreased by 21% and 50% in Ⅱ and Ⅲ, respectively, compared with that in Ⅰ. The DOC/SOC (soil organic carbon) ratios of 0-10 cm and 10-20 cm soil layers were significantly decreased by 27% and 43% after the conversion, respectively. In the 0-10 cm soil layer, the aromatic index and humification index of DOC in Ⅱ were significantly higher than that in Ⅲ. The infrared absorption ratio of soil DOC in the range of 3700-3000 cm-1, 1650-1620 cm-1, 1160-1000 cm-1, and 690-530 cm-1 in Ⅱ was higher than that in Ⅲ, indicating that the DOC in Ⅱ had higher carboxylic acids and aromatic substances than Ⅲ. The fluorescence index of DOC in Ⅱ and Ⅲ ranged from 1.4 to 1.9, and the biological index of Ⅱ was significantly higher than that of Ⅲ, indicating that Ⅲ had higher protein components in DOC and being more bioavailable. Thus, the differences of the content and structure of DOC between Ⅱ and Ⅲ might cause higher soil carbon pool of Ⅱ than that of Ⅲ.

Development and validation of a nomogram to predict the risk of death within 1 year in patients with non-ischemic dilated cardiomyopathy: a retrospective cohort study.

Predicting the chances mortality within 1 year in non-ischemic dilated cardiomyopathy patients can be very useful in clinical decision-making. This study has developed and validated a risk-prediction model for identifying factors contributing to mortality within 1 year in such patients. The predictive nomogram was constructed using a retrospective cohort study, with 615 of patients hospitalized in the First Affiliated Hospital of Guangxi Medical University between October 2012 and May 2020. A variety of factors, including presence of comorbidities, demographics, results of laboratory tests, echocardiography data, medication strategies, and instances of heart transplant or death were collected from electronic medical records and follow-up telephonic consultations. The least absolute shrinkage and selection operator and logistic regression analyses were used to identify the critical clinical factors for constructing the nomogram. Calibration, discrimination, and clinical usefulness of the predictive model were assessed using the calibration plot, C-index and decision curve analysis. Internal validation was assessed with bootstrapping validation. Among the patients from whom follow-up data were obtained, the incidence of an end event (deaths or heart transplantation within 1 year) was 171 cases per 1000 person-years (105 out of 615). The main predictors included in the nomogram were pulse pressure, red blood cell count, left ventricular end-diastolic dimension, levels of N-terminal pro b-type natriuretic peptide, medical history, in-hospital worsening heart failure, and use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The model showed excellent discrimination with a C-index of 0.839 (95% CI 0.799-0.879), and the calibration curve demonstrated good agreement. The C-index of internal validation was 0.826, which demonstrated that the model was quite efficacious. A decision curve analysis confirmed that our nomogram was clinically useful. In this study, we have developed a nomogram that can predict the risk of death within 1 year in patients with non-ischemic dilated cardiomyopathy. This will be useful in the early identification of patients in the terminal stages for better individualized clinical decisions.

[Effects of forest conversion on litterfall nutrient return and nutrient use efficiency in Mid-subtropical China.] / ä¸­äºšçƒ­å¸¦æ£®æž—è½¬æ¢å¯¹å‡‹è½ç‰©å »åˆ†å½’è¿˜åŠå »åˆ†åˆ©ç”¨æ•ˆçŽ‡çš„å½±å“.

To understand the impacts of mid-subtropical forest conversion on carbon and nutrient cycling, we conducted a 4-year investigation to examine litterfall, nutrient return and nutrient use efficiency of Castanopsis carlesii natural forest, C. carlesii secondary forest and Cunninghamia lanceolata plantation which were transformed from C. carlesii natural forest. The results showed that after C. carlesii natural forest was transformed into C. carlesii secon-dary forest and C. lanceolata plantation, the annual litter production decreased by 29.0% and 45.7%, nitrogen return of litter decreased by 34.0% and 72.7%, and phosphorus return decreased by 38.1% and 56.4%, respectively. The amount of carbon returned from litterfall in C. carlesii natural forest was 25.6% and 44.3% higher than that in C. carlesii secondary forest and C. lanceolata plantation, respectively. For C. lanceolata plantation, C. carlesii secondary forest and C. carlesii natural forest, nitrogen use efficiency of litterfall was 175.4, 94.8 and 92.0 kg·kg-1, respectively, and phosphorus use efficiency of litterfall was 3031.0, 2791.6 and 2537.2 kg·kg-1, respectively. It was concluded that C. lanceolata plantation was more limited by nitrogen compared with C. carlesii natural forest and secondary forest, and the effects of phosphorus limitation had similar effects on the three forests.

Mechanistic analysis of carbon-carbon bond formation by deoxypodophyllotoxin synthase.

Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS's catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel-Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.

Ultrafast attosecond-magnetic-field generation of the charge migration process based on HeH2+ and H2 + electronically excited by circularly polarized laser pulses.

The ultrafast process by the electron in molecular ions from one site or region to another that has come to be known as charge migration (CM), which is of fundamental importance to photon induced chemical or physical reactions. In this work, we study the electron current and ultrafast magnetic-field generation based on CM process of oriented asymmetric (HeH2+) and symmetric (H2 +) molecular ions. Calculated results show that they are ascribed to quantum interference of electronic states for these molecular ions under intense circularly polarized (CP) laser pulses. The two scenarios of (i) resonance excitation and (ii) direct ionization are considered through appropriately utilizing designed laser pulses. By comparison, the magnetic field induced by the scenario (i) is stronger than that of scenario (ii) for molecular ions. However, the scheme (ii) is very sensitive to the helicity of CP field, which is opposite to the scenario (i). Moreover, the magnetic field generated by H2 + is stronger than that by HeH2+ through scenario (i). Our findings provide a guiding principle for producing ultrafast magnetic fields in molecular systems for future research in ultrafast magneto-optics.

Antioxidant Activity of Novel Casein-Derived Peptides with Microbial Proteases as Characterized via Keap1-Nrf2 Pathway in HepG2 Cells.

Casein-derived antioxidant peptides by using microbial proteases have gained increasing attention. Combination of two microbial proteases, Protin SD-NY10 and Protease A "Amano" 2SD, was employed to hydrolyze casein to obtain potential antioxidant peptides that were identified by LCMS/ MS, chemically synthesized and characterized in a oxidatively damaged HepG2 cell model. Four peptides, YQLD, FSDIPNPIGSEN, FSDIPNPIGSE, YFYP were found to possess high 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability. Evaluation with HepG2 cells showed that the 4 peptides at low concentrations (< 1.0 mg/ml) protected the cells against oxidative damage. The 4 peptides exhibited different levels of antioxidant activity by stimulating mRNA and protein expression of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as nuclear factor erythroid-2-related factor 2 (Nrf2), but decreasing the mRNA expression of Kelch-like ECH-associated protein 1 (Keap1). Furthermore, these peptides decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), but increased glutathione (GSH) production in HepG2 cells. Therefore, the 4 casein-derived peptides obtained by using microbial proteases exhibited different antioxidant activity by activating the Keap1-Nrf2 signaling pathway, and they could serve as potential antioxidant agents in functional foods or pharmaceutic preparation.

[Effects of warming on soil inorganic nitrogen in the young and mature Cunninghamia lanceolata plantations in humid subtropical region, China]. / å¢žæ¸©å¯¹æ¹¿æ¶¦äºšçƒ­å¸¦æ‰æœ¨å¹¼æž—å’Œæˆç†Ÿæž—åœŸå£¤æ— æœºæ°®çš„å½±å“.

Soil nitrogen cycling in forests may be accelerated or inhibited by global warming, with consequences on forest productivity. Such an impact will be more complicated with extending period of warming. We examined the effects of warming on soil inorganic nitrogen content in the young and mature Cunninghamia lanceolata plantations. Warming was simulated by means of soil cable warming, simulating a future climate change scenario of 4 ℃ warming. The results showed that after three years warming, both total soil inorganic nitrogen and ammonium contents in the young and mature plantations were significantly reduced. The sharp decline occurred in the young plantation, with soil ammonium content in 0-10, 10-20, 20-40, 40-60 cm soil layers decreased by 32.1%, 37.1%, 20.8% and 19.9%, respectively. Dissolved organic nitrogen was reduced and N2O emission was accelerated in the both plantations. The main reasons for the reduction of soil inorganic nitrogen concentration were lower input of organic nitrogen substrate and higher gaseous nitrogen loss. The decrease in soil organic nitrogen substrate and increase in gaseous nitrogen emissions in the young plantation were larger than those in the mature plantation, indicating that soils in the young plantation were more sensitive to increasing temperature. The 3-year warming decreased soil inorganic nitrogen contents in the two C. lanceolata plantations, which might negatively affect productivity of the C. lanceolata plantations in subtropic China.

Association between serum angiopoietin-2 concentrations and periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

Angiopoietin-2 (Ang-2) is a proangiogenic factor that mediates inflammation and atherosclerosis. We evaluated the predictive value of circulating Ang-2 levels for periprocedural myocardial injury (PMI) in 145 patients undergoing elective percutaneous coronary intervention (PCI), and investigated whether post-PCI Ang-2 levels are influenced by PMI. PMI was defined as a post-procedural troponin elevation above the 5×99th percentile upper reference limit. Blood samples for Ang-2 analysis were collected at admission and on postoperative days 1 and 3. PMI occurred in 40 patients (28%). At baseline, there was no difference in Ang-2 levels between PMI and non-PMI patients (P=0.554). However, a significant interaction effect between PMI occurrence and time on Ang-2 levels was observed (interaction P=0.036). Although serum Ang-2 levels in non-PMI patients gradually decreased, Ang-2 levels in PMI patients did not change between different time-points. Multiple logistic regression analysis revealed that age, total stent length, and serum levels of N-terminal pro-brain natriuretic peptide were independent PMI predictors. These findings indicate that pre-procedural Ang-2 levels do not impact PMI occurrence after elective PCI. However, changes in Ang-2 levels after the procedure are closely related to PMI.

Natural products for treating colorectal cancer: A mechanistic review.

Colorectal cancer (CRC) is one of the most common types of cancers in humans and is closely linked to the global cancer-related mortalities worldwide. Molecular pathological epidemiology studies can reveal the risk factors of CRC and contribute to biomarker research and precision medicine. The current clinical treatment for CRC mainly involves surgery and chemotherapy. However, because of the occurrence of side effects and the emergence of drug resistance, there is an urgent need to find new and more effective drugs for CRC treatment. An increasing number of studies have demonstrated that many natural products possess effective anti-CRC effects and may serve as alternative chemotherapy agents for CRC treatment. In this review, we summarize the natural products with anti-CRC effects from different sources based on the chemical structures such as alkaloids, polysaccharides, polyphenols, terpenoid, unsaturated fatty acids, and discuss the natural product-derived drugs used clinically for colorectal cancer treatment. Furthermore, natural products of marine origin are also discussed for their enormous potential to serve as the candidate drugs. Notably, we generalize the experiment-based molecular mechanisms and the regulatory networks whereby natural products exert anticancer effects on cell proliferation, metastasis, apoptosis, autophagy, and angiogenesis.