Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

BACKGROUND AND PURPOSE: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). METHODS: This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. RESULTS: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. CONCLUSIONS: In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Genome-wide association analysis to search for new loci associated with stroke risk in Northwestern Chinese population.

BACKGROUND AND PURPOSE: Genetic factors play an important role in the pathogenesis of stroke(S). This study aimed to screen the loci associated with S risk in northwestern Chinese population by genome-wide association analysis (GWAS). METHODS: A total of 1394 subjects, including 682 S patients and 692 controls, were enrolled in this study. SPSS 25.0 software was used for statistical analysis, and the independent sample t-test as well as Chi-square test were used to analyze the differences in age and gender between the case and control groups. The Precision Medicine Diversity Array (PMDA) genotyping chip was used in this study. The genotyping platform was the Gene Titan multi-channel instrument, and the Axiom Analysis Suite 6.0 software was used for the data analyzing. Besides, the LASSO analysis, SNP-SNP and GO/KEGG analysis were conducted to analyze the association between significant loci and S risk. RESULTS: A total of 30 SNPs were found to be associated with the S risk based on additive model (p < 5 × 10-8). After the LASSO screening, 22 SNPs showed the diagnostic value in S. The SNPs interaction analysis further screened the SNP-SNP interaction groups associated with the S risk(p < 0.05). Finally, the GO/KEGG analysis discovered the suggestive significance loci could be involved in the S development mainly by immune-related functions and pathways. CONCLUSION: This study discovered 30 S related SNPs and analyzed the potential pathways associated with genes located on the 30 SNPs, which were beneficial for enriching the genetic mechanism analysis of S in northwestern Chinese population.

Causal association of type 2 diabetes with central retinal artery occlusion: a Mendelian randomization study.

Background: Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO. Methods: Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses. Results: Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221-3.638, P=7.423×10-3), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015-1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150-2.500; P=7.655×10-3), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015-1.812; P=0.039). Conclusion: Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO.

Ornidazole induced Stevens-Johnson syndrome without body surface involved: A case report.

RATIONALE: Ornidazole is a synthetic nitroimidazole derivative that is commonly prescribed for antiparasitic or anti-anaerobic infections. It is generally well tolerated, with known side effects including gastrointestinal tract, anaphylaxis, and central nervous system reactions. Ornidazole-induced binocular reactive keratitis and several mucocutaneous lesions have been rarely reported. PATIENT CONCERNS: A 52-year-old woman who suffered from vaginitis and received an ornidazole vaginal plug (0.5 g). Approximately 20 minutes after the suppository was inserted into the vagina, her lips were swollen and valva and labia were burning. Her eyes were red, sore, and watery. DIAGNOSIS: She was diagnosed as Steven-Johnson syndrome by the ophthalmologist. According to the Naranjo scale, the adverse drug reaction was evaluated to be probable and severe. INTERVENTIONS: Dexamethasone was intravenous administrated as anti-inflammatory therapy for 10 days. Eye drops were locally given to relieve edema and promote healing of the epithelium. The symptoms of her eyes, lips, vulva and crissum were soon relieved. OUTCOMES: The patient was discharge from hospital with improved symptoms. LESSONS: In order to avoid severe adverse effect, the patient should not use metronidazole ether orally or vaginally. The case emphasized the importance of rapid and accurate diagnosis of Steven-Johnson syndrome induced by ornidazole vaginal plug, especially when the eye symptoms were the chief complaint without body skin involved.

Association of baseline fasting plasma glucose with 1-year mortality in non-diabetic patients with acute cerebral infarction: a multicentre observational cohort study.

OBJECTIVES: Evidence on the association between fasting blood glucose and mortality in non-diabetic patients who had a stroke is limited. We aimed to investigate the association of baseline fasting plasma glucose (FPG) with 1 year all-cause mortality in non-diabetic patients with acute cerebral infarction (ACI). DESIGN: A multicentre prospective cohort study. SETTING: Four grade A tertiary hospitals in the Xi'an district of China. PARTICIPANTS: A total of 1496 non-diabetic patients within 7 days of ACI were included. MAIN OUTCOME MEASURES: The outcome was 1 year all-cause mortality. Baseline FPG was analysed as a continuous variable and was divided into four quartiles (group Q1-group Q4). We used multivariable Cox regression analyses, curve fitting and Kaplan-Meier (K-M) analyses to explore the association of baseline FPG with 1 year all-cause mortality in non-diabetic patients with ACI. RESULTS: After controlling for confounders, multivariable Cox regression analyses indicated a 17% increase in 1 year all-cause mortality for every 1 mmol/L of baseline FPG increase (HR=1.17, 95% CI 1.02 to 1.35, p=0.030). Patients from the Q4 group had 2.08 times increased hazard of 1 year all-cause mortality compared with the Q1 group (HR=2.08, 95% CI 1.13 to 3.82, p=0.019), while the survival rate of patients in group Q4 was decreased compared with that in other groups (p<0.001). The curve fitting revealed a positive but non-linear association of baseline FPG with 1-year all-cause mortality in non-diabetic patients with ACI. CONCLUSION: In non-diabetic patients with ACI, elevated baseline FPG is an independent risk factor for 1-year all-cause mortality, and the two are positively and non-linearly associated. These results suggest that high FPG should be seen as a concern in non-diabetic patients with ACI.

Biological functions and molecular subtypes regulated by miR-142-3p in colon cancer.

MicroRNA-142-3p (miR-142-3p) has been reported to be implicated in colon cancer; however, the possible regulatory mechanisms and molecular subtypes regulated by miR-142-3p have not been fully elucidated. This study aimed to investigate the biological functions and regulatory mechanism of miR-142-3p in colon cancer. The expression level of miR-142-3p in colon cancer was analyzed based on the mRNA and miRNA expression datasets of colon cancer retrieved from The Cancer Genome Atlas. Target genes of miR-142-3p were also predicted. Based on these target genes, the functions and subtypes of miR-142-3p were investigated. The metabolic and tumor-related pathways, immune microenvironment, and target gene expression between the 2 subtypes were analyzed. MiR-142-3p was upregulated in tumor tissues, and its high expression indicated a poor prognosis. A total of 39 target genes were predicted, which were significantly involved in autophagy- and metabolism-related functions and pathways. Based on these target genes, the colon cancer samples were clustered into 2 subtypes. There were 35 metabolism-related pathways that were significantly different between the 2 clusters. The immune and stromal scores in cluster 2 were higher than those in cluster 1, whereas the tumor purity of cluster 2 was significantly lower than that of cluster 1. TP53INP2 expression in cluster 2 was higher than that in cluster 1. MiR-142-3p may promote colon cancer progression via autophagy- and metabolism-related pathways. MiR-142-3p may be served as a candidate target for the treatment of colon cancer.

Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi'an Stroke Registry Study of China.

INTRODUCTION: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. METHODS: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. RESULTS: Among 2,288 participants, the mean TyG index was 8.8  0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98-2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09-7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. CONCLUSION: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients.

Elevated non-HDL-C/HDL-C ratio increases the 1-year risk of recurrent stroke in older patients with non-disabling ischemic cerebrovascular events: results from the Xi'an Stroke Registry Study of China.

BACKGROUND: Few studies have explored the prognostic role of nontraditional lipid-related indicators in non-disabling ischemic cerebrovascular events (NICE). In this study, we aimed to investigate the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and the1-year risk of recurrent stroke in patients with NICE. METHODS: Total cholesterol (TC), HDL-C, and patient information were collected at admission. Recurrent stroke events were followed up 3, 6, and 12 months after onset. Non-HDL-C levels were calculated by subtracting HDL-C from TC. The non-HDL-C/HDL-C ratio was treated as a continuous variable and in quartiles (Q1-Q4). Stratified multivariate Cox regression was used to investigate the relationship between the non-HDL-C/HDL-C ratio and the 1-year risk of recurrent stroke in patients with NICE. RESULTS: Overall, 1,659 patients with NICE were enrolled. For each unit increase in the non-HDL-C/HDL-C ratio, the 1-year risk of recurrent stroke in patients aged ≥ 65 years (older patients) with NICE increased by 64% in the adjusted model (hazard ratio [HR]: 1.64, 95%confidence interval [CI]:1.18-2.27, P = 0.003), and the HRs were 3.21 and 4.24 times higher in the Q3 and Q4 groups than that in the Q1 group, which was considered to be the reference (adjusted model Q3: HR: 3.21, 95%CI: 1.05-9.83, P = 0.041; adjusted model Q4: HR: 4.24, 95%CI: 1.30-13.85, P = 0.017). However, there was no significant difference in patients younger than 65 years. Both curve fitting and Kaplan-Meier cumulative risk analysis showed that an elevated non-HDL-C/HDL-C ratio significantly increased the 1-year risk of recurrent stroke in older patients with NICE. The optimal range for the non-HDL-C/HDL-C ratio should be no higher than the Q2 group (2.256-2.939). Stratified Cox regression analysis showed that these results tended to be stable for different comorbidities (all P for interaction > 0.05). CONCLUSIONS: Elevated non-HDL-C/HDL-C ratios significantly increased the 1-year risk of recurrent stroke in older patients with NICE. Therefore, clinicians need to pay more attention to this indicator when managing older patients with NICE.

Serum homocysteine level is an independent risk factor for 1-year stroke recurrence in patients with acute ischemic stroke and H-type hypertension: results from the Xi'an stroke registry study of China.

Background: H-type hypertension has a high prevalence in China. However, the association of serum homocysteine levels with 1-year stroke recurrence in patients with acute ischemic stroke (AIS) and H-type hypertension has not been studied. Methods: A prospective cohort study of patients with AIS admitted to hospitals between January and December 2015 in Xi'an, China, was conducted. Serum homocysteine levels, demographic data, and other relevant information were collected from all patients upon admission. Stroke recurrences were routinely tracked at 1, 3, 6, and 12 months after discharge. The blood homocysteine level was studied as a continuous variable and tertiles (T1-T3). A multivariable Cox proportional hazard model and a two-piecewise linear regression model were utilized to evaluate the association and ascertain the threshold effect regarding the serum homocysteine level and 1-year stroke recurrence in patients with AIS and H-type hypertension. Results: Overall, 951 patients with AIS and H-type hypertension were enrolled, of whom 61.1% were male. After adjusting for confounders, patients in T3 had a significantly increased risk of recurrent stroke within 1 year, compared with those in T1 as the reference (hazard ratio = 2.24, 95% confidence interval: 1.01-4.97, p = 0.047). Curve fitting showed that serum homocysteine levels were positively curvilinearly correlated with 1-year stroke recurrence. Threshold effect analysis showed that an optimal threshold of serum homocysteine level <25 µmol/L was effective in reducing the risk of 1-year stroke recurrence in patients with AIS and H-type hypertension. Elevated homocysteine levels in patients with severe neurological deficits on admission significantly increased the risk of 1-year stroke recurrence (p for interaction = 0.041). Conclusions: In patients with AIS and H-type hypertension, the serum homocysteine level was an independent risk factor for 1-year stroke recurrence. A serum homocysteine level of ≥25 µmol/L significantly increased the risk of 1-year stroke recurrence. These findings can inform the creation of a more precise homocysteine reference range for the prevention and treatment of 1-year stroke recurrence in patients with AIS and H-type hypertension and provide a theoretical foundation for the individualized prevention and treatment of stroke recurrence.

Plasma lncRNA LIPCAR Expression Levels Associated with Neurological Impairment and Stroke Subtypes in Patients with Acute Cerebral Infarction: A Prospective Observational Study with a Control Group.

INTRODUCTION: This prospective observational study with a control group aimed to compare the plasma levels of long non-coding RNA (lncRNA) LIPCAR between patients with acute cerebral infarction (ACI) and healthy controls, and to assess the prognostic abilities of LIPCAR for adverse outcomes of patients with ACI at 1-year follow-up. METHODS: Eighty patients with ACI, of whom 40 had large artery atherosclerosis (LAA) and 40 had cardioembolism (CE) and who were hospitalized at Xi'an No. 1 Hospital from July 2019 to June 2020, were selected as the case group. Age- and sex-matched non-stroke patients from the same hospital throughout the same time period were chosen as the control group. Real-time quantitative reverse transcription polymerase chain reaction was used to measure the levels of plasma lncRNA LIPCAR. The correlations of LIPCAR expression among the LAA, CE, and control groups were assessed using Spearman's correlation analysis. Curve fitting and multivariate logistic regression were used to analyze the LIPCAR levels and 1-year adverse outcomes of patients with ACI and its subtypes. RESULTS: The expression of plasma LIPCAR in the case group was noticeably higher than that of the control group (2.42 ± 1.49 vs. 1.00 ± 0.47, p < 0.001). Patients with CE had considerably higher levels of LIPCAR expression than those with LAA. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly positively correlated with LIPCAR expression in patients with CE and LAA. Furthermore, the correlation was stronger in patients with CE than in those with LAA, with correlation coefficients of 0.69 and 0.64, respectively. Curve fitting revealed a non-linear correlation between LIPCAR expression levels, 1-year recurrent stroke, all-cause mortalities, and poor prognoses, with a cut-off value of 2.2. CONCLUSION: The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and CE subtype in patients with ACI. Increased 1-year risk of adverse outcomes may be associated with high levels of LIPCAR expression.

Acute cerebral infarction is the second-leading cause of death worldwide. Therefore, available diagnostic and prognostic tools are of the utmost importance. It is easy to acquire hematologic biomarkers and to provide direct information related to the severity of brain injury and the risk of stroke. However, it has been shown that the study of hematologic markers in aspects of both identifying stroke subtypes and predicting neurological impairment are still few and imperfect in clinical application of stroke prognosis. The long non-coding RNA LIPCAR plays an important role in the pathophysiology of cardiovascular disease. Nonetheless, to date, no exploration has been carried out on the correlation between lncRNA LIPCAR, severity on admission, and prognosis of stroke subtypes. Thus, this study aimed to investigate the plasma levels of lncRNA LIPCAR expression and their correlations in patients with acute cerebral infarction and its subtypes. Our results show that the plasma levels of LIPCAR expression of the patients with acute cerebral infarction were noticeably higher than those of the non-stroke control patients. Patients with cardioembolism subtype had considerably higher levels of LIPCAR expression than those with large artery atherosclerosis. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly correlated with LIPCAR expression in patients with cardioembolism and large artery atherosclerosis; the correlation was stronger in patients with cardioembolism than in patients with large artery atherosclerosis, with correlation coefficients of 0.69 and 0.64, respectively. Furthermore, curve fitting revealed a non-linear correlation between LIPCAR expression levels and 1-year outcome events. The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and cardioembolism subtype in patients with acute cerebral infarction.

Cochlear-implant Mandarin tone recognition with a disyllabic word corpus.

Despite pitch being considered the primary cue for discriminating lexical tones, there are secondary cues such as loudness contour and duration, which may allow some cochlear implant (CI) tone discrimination even with severely degraded pitch cues. To isolate pitch cues from other cues, we developed a new disyllabic word stimulus set (Di) whose primary (pitch) and secondary (loudness) cue varied independently. This Di set consists of 270 disyllabic words, each having a distinct meaning depending on the perceived tone. Thus, listeners who hear the primary pitch cue clearly may hear a different meaning from listeners who struggle with the pitch cue and must rely on the secondary loudness contour. A lexical tone recognition experiment was conducted, which compared Di with a monosyllabic set of natural recordings. Seventeen CI users and eight normal-hearing (NH) listeners took part in the experiment. Results showed that CI users had poorer pitch cues encoding and their tone recognition performance was significantly influenced by the "missing" or "confusing" secondary cues with the Di corpus. The pitch-contour-based tone recognition is still far from satisfactory for CI users compared to NH listeners, even if some appear to integrate multiple cues to achieve high scores. This disyllabic corpus could be used to examine the performance of pitch recognition of CI users and the effectiveness of pitch cue enhancement based Mandarin tone enhancement strategies. The Di corpus is freely available online: https://github.com/BetterCI/DiTone.

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.

Objective: Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. Methods: By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Results: Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. Conclusions: The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.

Non-Linear Association Between Serum Alkaline Phosphatase and 3-Month Outcomes in Patients With Acute Stroke: Results From the Xi'an Stroke Registry Study of China.

Background: Alkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China. Methods: We enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1-Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3-6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes. Results: Overall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19-3.96; P = 0.011] and patients in Q3 (76.8-92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14-0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0-76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes. Conclusion: Non-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.

Efficacy of Methionine-Restricted Diets on Cancers In Vivo.

Methionine (MET) dependence is the elevated requirement of cancer cells for MET. Cancer cells are arrested when MET is restricted in late S/G2 phase of the cell cycle. MET dependence may be the only known general metabolic defect in cancer. This chapter reviews the in vivo efficacy of dietary MET restriction (MR) to arrest human-cancer cell-line tumors and mouse tumors in nude mice. Human cancer xenografts in nude mice, when fed a MET-free diet, had greatly inhibited tumor growth. The body weight of mice on the MET-free diet was found to be maintainable by once-per-week administration of MET. These results suggested that MET dependence can be an important target for human cancer treatment. Yoshida sarcoma in nude mice on a MET-depleted diet regressed. MET depletion resulted in the extended survival of the tumor-bearing mice. These experiments are a prelude to further clinical studies of the efficacy of MR diets on cancer patients.

Complete mitochondrial genome of the Nigeria-Cameroon chimpanzee, Pan troglodytes ellioti (Primates: Hominidae).

Chimpanzees are especially suited to teach us about ourselves, both in terms of their similarities and differences with human, and such important similarities and differences have also been noted for the incidence and severity of several major human diseases. In the present work, we report the entire mitochondrial genome of the Nigeria-Cameroon chimpanzee (Pan troglodytes ellioti) for the first time. Results shows that this mitogenome is 16,559 bp long and consists of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 putative non-coding region (D-loop region). The genomic organization and gene order are the same as other Chimpanzees. The whole nucleotide base composition is 31.1% of A, 30.7% of C, 12.9% G, and 25.3% T, with a slight A+T bias of 56.4%. Most of the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes. The complete mitochondrial genome sequence reported here provides useful genetic information for P. t. ellioti, and will further contribute to the comparative genomics studies in primates.

Tailoring the electronic structure of ß-Ga2O3 by non-metal doping from hybrid density functional theory calculations.

A systematic study using density functional theory has been performed for ß-Ga2O3 doped with non-metal elements X (X = C, N, F, Si, P, S, Cl, Se, Br, and I) to evaluate the effect of doping on the band edges and photocatalytic activity of ß-Ga2O3. The utilization of a more reliable hybrid density functional, as prescribed by Heyd, Scuseria and Ernzerhof, is found to be effective in predicting the band gap of ß-Ga2O3 (4.5 eV), in agreement with the experimental result (4.59 eV). Based on the relaxed structures of X-doped systems, the defect formation energies and the plots of density of states have been calculated to analyze the band edges, the band gap states and the preferred doping sites. Our results show that the doping is energetically favored under Ga-rich growth conditions with respect to O-rich growth conditions. It is easier to replace the threefold coordinated O atom with non-metal elements compared to the fourfold coordinated O atom. X-doped systems (X = C, Si, P) show no change in the band gap, with the presence of discrete midgap states, which have adverse effect on the photocatalytic properties. The photocatalytic redox ability can be improved to a certain extent by doping with N, S, Cl, Se, Br, and I. The band alignments for Se-doped and I-doped ß-Ga2O3 are well positioned for the feasibility of both photo-oxidation and photo-reduction of water, which are promising photocatalysts for water splitting in the visible region.

Mating experience and food deprivation modulate odor preference and dispersal in Drosophila melanogaster males.

Rotting fruits offer all of the known resources required for the livelihood of Drosophila melanogaster Meigen (Diptera: Drosophilidae). During fruit fermentation, carbohydrates and proteins are decomposed to produce volatile alcohols and amines, respectively. It is hypothesized that D. melanogaster adults can detect these chemical cues at a distance to identify and locate the decaying fruits. In the present paper, we compared the olfactory responses and movement of male flies varying in mating status and nutritional state to methanol, ethanol, and ammonia sources using a glass Y-tube olfactometer. In general, ethanol vapor at low to moderate concentrations repelled more hungry mated males than satiated ones. In contrast, methanol showed little difference in the attractiveness to males at different nutritional states and mating status. Moreover, ammonia attracted more hungry mated males. The attractiveness increased almost linearly with ammonia concentration from lowest to highest. When ammonia and artificial diet were put together in the odor arm, the responses of male flies to mixed odor mimicked the response to ammonia. Furthermore, odorant concentration, mating status, and nutritional state affected the flies' dispersal. Mated and starved males dispersed at a higher rate than virgin and satiated ones. Thus, our results showed that starved, mated males increased dispersal and preferred ammonia that originated from protein.

RNAi suppression of the ryanodine receptor gene results in decreased susceptibility to chlorantraniliprole in Colorado potato beetle Leptinotarsa decemlineata.

Leptinotarsadecemlineata is the most important pest in potato and causes serious yield loss each year. Chlorantraniliprole acts on insect ryanodine receptors (RyRs) and is among the most active compounds against L. decemlineata. Here we cloned and characterized a 15,792-bp full-length LdRyR cDNA that encoded a 5128-amino acid protein. LdRyR shares 85-92% amino acid similarities with other insect RyR homologues, and 59-61% similarities with those from Caenorhabditis elegans and Homo sapiens. All hallmarks of the RyR proteins are conserved in LdRyR. LdRyR has a MIR domain, two RIH domains, three SPRY domains, four copies of RyR domain and a RIH-associated domain in the N-terminus, and it possesses two consensus calcium ion-binding EF-hand motifs and six predicted transmembrane helices in the C-terminus. Temporal, spatial and tissue-specific expression patterns of LdRyR were evaluated. LdRyR expression level was increased constantly from egg to wandering stages, dropped in pupal stage and was increased again in the adult stage. It was widely expressed in the head, thorax and abdomen of day 3 fourth-instar larvae. Moreover, it was ubiquitously expressed in all inspected tissues including epidermis, foregut, midgut, ileum, rectum, fat body, ventral ganglia and Malpighian tubules in day 3 fourth-instar larvae. Dietary introduction of double-stranded RNA of LdRyR significantly reduced the mRNA levels of the target gene in the larvae and adults, respectively, and significantly decreased chlorantraniliprole-induced mortalities. Thus, our results suggested that LdRyR encoded a functional ryanodine receptor in L. decemlineata.

Thin-layer chromatographic identification of Chinese propolis using chemometric fingerprinting.

INTRODUCTION: Poplar tree gum has a similar chemical composition and appearance to Chinese propolis (bee glue) and has been widely used as a counterfeit propolis because Chinese propolis is typically the poplar-type propolis, the chemical composition of which is determined mainly by the resin of poplar trees. The discrimination of Chinese propolis from poplar tree gum is a challenging task. OBJECTIVE: To develop a rapid thin-layer chromatographic (TLC) identification method using chemometric fingerprinting to discriminate Chinese propolis from poplar tree gum. METHODS: A new TLC method using a combination of ammonia and hydrogen peroxide vapours as the visualisation reagent was developed to characterise the chemical profile of Chinese propolis. Three separate people performed TLC on eight Chinese propolis samples and three poplar tree gum samples of varying origins. Five chemometric methods, including similarity analysis, hierarchical clustering, k-means clustering, neural network and support vector machine, were compared for use in classifying the samples based on their densitograms obtained from the TLC chromatograms via image analysis. RESULTS: Hierarchical clustering, neural network and support vector machine analyses achieved a correct classification rate of 100% in classifying the samples. A strategy for TLC identification of Chinese propolis using chemometric fingerprinting was proposed and it provided accurate sample classification. CONCLUSION: The study has shown that the TLC identification method using chemometric fingerprinting is a rapid, low-cost method for the discrimination of Chinese propolis from poplar tree gum and may be used for the quality control of Chinese propolis.

[Association of genetic variant in 12-lipoxygenase and risk of hepatic carcinoma].

OBJECTIVE: To explore the association of 12-lipoxygenase (LOX12) Arg261Gln polymorphism with the risk of hepatic carcinoma in Chinese population. METHODS: A total of 280 cases of hepatic carcinoma and 560 frequency-matched controls were recruited from January 2008 to December 2012 at Hebei United University Affiliated Hospital. The method of PCR-restriction fragment length polymorphism (RFLP) was employed to genotype LOX12 Arg261Gln polymorphism. And odds ratios (OR) and 95% confidence intervals (CI) were calculated with a model of unconditional Logistic regression. RESULTS: The allelic frequency for LOX12 Arg261Gln was significantly higher in hepatic carcinoma cases than that in controls (0.563 vs 0.437). For the control group, the three genotypes of LOX12 Arg/Arg, Arg/Gln and Gln/Gln were 24.3% (136/560), 52.9% (296/560) and 22.8% (128/560) respectively. For the hepatic carcinoma group, these three genotypes were 19.1% (53/278), 49.3% (137/278) and 31.6% (88/278) respectively. Logistic regression analysis showed that, compared with 261 Arg/Arg genotype carriers, the subjects with 261Gln/Gln had increased risks for hepatic carcinoma (OR = 1.83, 95%CI:1.18-2.84). When stratified by smoking status, the 261Gln/Gln carriers had an increased risk of developing hepatic carcinoma (OR = 2.23, 95%CI:1.16-4.26) among smokers, but not among non-smokers. CONCLUSION: LOX12 Arg261Gln polymorphism is associated with the susceptibility to hepatic carcinoma.