The crane fly glycosylated triketide δ-lactone cornicinine elicits akinete differentiation of the cyanobiont in aquatic Azolla fern symbioses.

The restriction of plant-symbiont dinitrogen fixation by an insect semiochemical had not been previously described. Here we report on a glycosylated triketide δ-lactone from Nephrotoma cornicina crane flies, cornicinine, that causes chlorosis in the floating-fern symbioses from the genus Azolla. Only the glycosylated trans-A form of chemically synthesized cornicinine was active: 500 nM cornicinine in the growth medium turned all cyanobacterial filaments from Nostoc azollae inside the host leaf-cavities into akinetes typically secreting CTB-bacteriocins. Cornicinine further inhibited akinete germination in Azolla sporelings, precluding re-establishment of the symbiosis during sexual reproduction. It did not impact development of the plant Arabidopsis thaliana or several free-living cyanobacteria from the genera Anabaena or Nostoc but affected the fern host without cyanobiont. Fern-host mRNA sequencing from isolated leaf cavities confirmed high NH4-assimilation and proanthocyanidin biosynthesis in this trichome-rich tissue. After cornicinine treatment, it revealed activation of Cullin-RING ubiquitin-ligase-pathways, known to mediate metabolite signaling and plant elicitation consistent with the chlorosis phenotype, and increased JA-oxidase, sulfate transport and exosome formation. The work begins to uncover molecular mechanisms of cyanobiont differentiation in a seed-free plant symbiosis important for wetland ecology or circular crop-production today, that once caused massive CO2 draw-down during the Eocene geological past.

Enhancing astaxanthin biosynthesis and pathway expansion towards glycosylated C40 carotenoids by Corynebacterium glutamicum.

Astaxanthin, a versatile C40 carotenoid prized for its applications in food, cosmetics, and health, is a bright red pigment with powerful antioxidant properties. To enhance astaxanthin production in Corynebacterium glutamicum, we employed rational pathway engineering strategies, focused on improving precursor availability and optimizing terminal oxy-functionalized C40 carotenoid biosynthesis. Our efforts resulted in an increased astaxanthin precursor supply with 1.5-fold higher ß-carotene production with strain BETA6 (18 mg g-1 CDW). Further advancements in astaxanthin production were made by fine-tuning the expression of the ß-carotene hydroxylase gene crtZ and ß-carotene ketolase gene crtW, yielding a nearly fivefold increase in astaxanthin (strain ASTA**), with astaxanthin constituting 72% of total carotenoids. ASTA** was successfully transferred to a 2 L fed-batch fermentation with an enhanced titer of 103 mg L-1 astaxanthin with a volumetric productivity of 1.5 mg L-1 h-1. Based on this strain a pathway expansion was achieved towards glycosylated C40 carotenoids under heterologous expression of the glycosyltransferase gene crtX. To the best of our knowledge, this is the first time astaxanthin-ß-D-diglucoside was produced with C. glutamicum achieving high titers of microbial C40 glucosides of 39 mg L-1. This study showcases the potential of pathway engineering to unlock novel C40 carotenoid variants for diverse industrial applications.

The Impact of Resistance Exercise Training on Glycemic Control Among Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The prevalence of type 2 diabetes mellitus (T2DM) presents a challenge for health organizations because of its high likelihood of morbidity and mortality. There is an increasing body of evidence exploring the efficacy of resistance training (RT) alone on glycemic control. Objective: To update the effectiveness of RT on glycosylated hemoglobin (HbA1c) and fasting glucose in adults diagnosed with T2DM. Methods: CINAHL (EBSDCO), PubMed, MEDLINE (Ovid), and EMBASE (Ovid) databases were searched from inception to 30 January 2024. Published randomized controlled trials (RCTs) of adult humans with T2DM assessing the impact of RT on HbA1c and fasting glucose compared with control condition were included. Data were pooled by the inverse-variance method and reported as mean differences (MDs) with 95% confidence intervals (CIs). Results: Forty-six RCTs totaling 2130 participants met the inclusion criteria. Meta-analysis demonstrated RT significantly reduced HbA1c (MD -0.50% [95% CI, -0.67, -0.34 %], p < .00,001) and fasting glucose (MD -12.03 mg/dl [95% CI, -19.36, -4.69 mg/dl], p = .001). Subgroup analyses found that exercise training durations, gender, and risk of bias had statistically significant effects on HbA1c levels and fasting glucose concentrations after resistance training. However, meta-regression analyses revealed that variables including year of publication, number of sessions per week, mean sample age, sample size, and study quality scores did not significantly affect the change in either HbA1c or glucose. Conclusion: Our meta-analysis with meta-regression delivers further evidence that RT programs are effective approach in attenuation of HbA1c and fasting glucose in individuals with T2DM.

Poor Prestroke Glycemic Control Increases the Rate of Symptomatic Intracranial Hemorrhage after Mechanical Thrombectomy.

(1) Background: Diabetes is a well-established risk factor for acute ischemic stroke (AIS). This study evaluated the impact of prestroke glycemic control in diabetic patients on their 3-month clinical outcome after mechanical thrombectomy (MT). (2) Methods: AIS patients with a premorbid modified Rankin scale (mRS) score of 0-2 who were admitted within 6 h after stroke onset and treated with MT between January 2020 and August 2023 were retrospectively analyzed. The study evaluated the effect of prestroke glycemic control on the stroke severity, reperfusion rate, symptomatic intracranial hemorrhage (sICH) and favorable clinical outcome (modified Rankin scale score 0-2) at 3 months after endovascular treatment. (3) Results: A total of 364 patients were analyzed, with 275 cases of non-diabetes (ND), 66 of well-controlled diabetes (WCD) and 23 of poorly controlled diabetes (PCD). There was no significant difference in the baseline neurological deficit expressed according to the National Institutes of Health Stroke Scale among the three groups. The time from stroke onset to groin puncture was similar in the ND, WCD and PCD groups (median 215 min, 194.5 min and 222.5 min, respectively). There was no significant difference in the favorable 3-month clinical outcomes among these three groups (35.2% of ND patients, 42.4% of WCD patients and 39.1% of PCD patients) or full recovery (12.4% of ND patients, 11.0% of WCD patients and 17.4% of PCD patients). The rate of sICH was significantly higher in the PCD group as compared to the ND and WDP groups (21.7% of PCD patients versus 7.6% of ND patients, p = 0.038, and 6.0% of WCD patients, p = 0.046), but the 3-month mortality did not differ between the three groups (21.8% of ND group, 19.7% of WCD group and 26.1% of PCD group). (4) Conclusions: This study shows that poor prestroke glycemic control in AIS diabetic patients does not change the chance of a good clinical functional outcome after endovascular treatment. However, the increased risk of hemorrhagic complications in this group of patients should be considered.

Prediction of glycosylated hemoglobin level in patients with cardiovascular diseases and type 2 diabetes mellitus with respect to anti-diabetic medication.

Blood glycosylated hemoglobin level can be affected by various factors in patients with type 2 diabetes and cardiovascular diseases. Frequent measurements are expensive, and a suitable estimation method could improve treatment outcomes. Patients and methods: 93 patients were recruited in this research. We analyzed a number of parameters such as age, glucose level, blood pressure, Body Mass Index, cholesterol level, echocardiography et al. Patients were prescribed metformin. One group (n=60) additionally was taking sitagliptin. We applied eight machine learning methods (k nearest neighbors, Random Forest, Support Vector Machine, Extra Trees, XGBoost, Linear Regression including Lasso, and ElasticNet) to predict exact values of glycosylated hemoglobin in two years. Results: We applied a feature selection approach using step-by-step removal of them, Linear Regression on remaining features, and Pearson's correlation coefficient on the validation set. As a result, we got four different subsets for each group. We compared all eight Machine Learning methods using different hyperparameters on validation sets and chose the best models. We tested the best models on the external testing set and got R2 = 0.88, C Index = 0.857, Accuracy = 0.846, and MAE (Mean Absolute Error) = 0.65 for the first group, R2 = 0.86, C Index = 0.80, Accuracy = 0.75, and MAE = 0.41 for the second group. Conclusion: The resulting algorithms could be used to assist clinical decision-making on prescribing anti-diabetic medications in pursuit of achieving glycemic control.

Gender effect of glucose, insulin/glucagon ratio, lipids, and nitrogen-metabolites on serum HGF and EGF levels in patients with diabetes type 2.

Hepatocyte growth factor (HGF) exhibits potent growth-inducing properties across various tissues, while epidermal growth factor (EGF) acts as a molecular integration point for diverse stimuli. HGF plays a crucial role in hepatic metabolism, tissue repair, and offers protective effects on epithelial and non-epithelial organs, in addition to its involvement in reducing apoptosis and inflammation, underscoring its anti-inflammatory capabilities. The HGF-Met system is instrumental in hepatic metabolism and enhancing insulin sensitivity in animal diabetes models. Similarly, the EGF and its receptor tyrosine kinase family (EGFR) are critical in regulating cell growth, proliferation, migration, and differentiation in both healthy and diseased states, with EGF also contributing to insulin sensitivity. In this observational study, we aimed to identify correlations between serum levels of HGF and EGF, insulin, glucagon, glucose, and primary serum lipids in patients with type 2 diabetes mellitus (DM), taking into account the impact of gender. We noted differences in the management of glucose, insulin, and glucagon between healthy men and women, potentially due to the distinct influences of sexual hormones on the development of type 2 DM. Additionally, metabolites such as glucose, albumin, direct bilirubin, nitrites, and ammonia might influence serum levels of growth factors and hormones. In summary, our results highlight the regulatory role of insulin and glucagon in serum glucose and lipids, along with variations in HGF and EGF levels, which are affected by gender. This link is especially significant in DM, where impaired cell proliferation or repair mechanisms lead to metabolic changes. The gender-based differences in growth factors point to their involvement in the pathophysiology of the disease.

Gestational Diabetes and Subsequent Metabolic Dysfunction: An National Health and Nutrition Examination Survey Analysis (2011-2018).

Background: Gestational diabetes mellitus (GDM) complicates ∼10% of pregnancies, with the highest rates among Asian women. Evidence suggests that GDM is associated with an increased risk for future chronic health conditions, yet data for Asian women are sparse. We explored the association between prior GDM and metabolic dysfunction with nationally representative data to obtain Asian-specific estimates. Methods: For this cross-sectional study, data were drawn from the National Health and Nutrition Examination Survey for 7195 women with a prior pregnancy. GDM (yes/no) was defined using the question "During pregnancy, were you ever told by a doctor or other health professional that you had diabetes, sugar diabetes, or gestational diabetes?." Current metabolic dysfunction (yes/no) was based on having at least one of four indicators: systolic blood pressure (SBP, ≥130 mmHg), waist circumference (≥88 cm), high-density lipoprotein (HDL) cholesterol (<50 mg/dL), and glycosylated hemoglobin (HbA1c) (≥6.5%). Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between prior GDM and metabolic outcomes, overall and by race. Models included sampling weights and demographic and behavioral factors. Results: Overall, women with prior GDM had 46% greater odds of high waist circumference (OR: 1.5; 95% CI: 1.1-2.0) and 200% greater odds (OR: 3.0; 95% CI: 2.1-4.2) of high HbA1c. Prior GDM was not associated with high blood pressure or low HDL cholesterol. In race-specific analyses, prior GDM was associated with increased risk of elevated HbA1c among Asian (OR: 6.6; 95% CI: 2.5-17.2), Mexican American (OR: 3.0; 95% CI: 1.5-5.8), Black (OR: 3.0; 95% CI: 1.7-5.5), and White (OR: 2.6; 95% CI: 1.5-4.6) women. Prior GDM was associated with elevated SBP among Mexican American women and low HDL among Black women. Discussion: Prior GDM is associated with elevated HbA1c among all women, yet is a stronger predictor of elevated HbA1c among Asian women than other women. Race-specific associations between prior GDM and metabolic dysfunction were observed among Mexican American and Black women. Further research is warranted to understand the observed race/ethnic-specific associations.

Management of intervenable factors to reduce vascular complications in patients with internal carotid artery occlusion treated by non-emergency endovascular treatment.

Objective: This study aims to identify risk factors for vascular complications during non-emergency endovascular treatment in patients with internal carotid artery occlusion (ICAO) and to propose potential interventions. Method: A retrospective analysis of 92 patients with ICAO who received non-emergency endovascular treatment in our center from 1 January 2018 to 31 June 2023, was conducted. The correlation between intraoperative vascular complications and potential risk factors was studied, and interaction analysis was performed. Results: Our findings revealed that the use of non-neurology guide wires to open vessels (adjusted OR: 4.1, 95%CI: 1.3-12.8; p = 0.014) and glycosylated hemoglobin (HbA1c) ≥ 6.5 mmol/L (adjusted OR: 3.2, 95%CI: 1.2-8.9; p = 0.023) was significantly associated with vascular complications in non-emergency endovascular treatment of ICAO patients. The restricted cubic spline (RCS) showed that the higher the HbA1c level, the higher the risk of vascular complications. Conclusion: The use of non-neurology guide wires for vessel opening during non-emergency endovascular treatment in patients with ICAO increases the risk of vascular complications. Preoperative assessment and management of HbA1c levels can reduce the incidence of intraoperative vascular complications.

Adiponectin and HbA1c levels among Indian patients with diabetes mellitus.

Adiponectin is closely related to glucose metabolism and newly diagnosed type 2 diabetes mellitus (T2DM), and other kinds of diabetes linked to the risk of T2DM. Therefore, it is of interest to report the correlation between adiponectin levels and glycosylated hemoglobin (HbA1c) as a diagnostic marker of T2DM and healthy control. Total 210 participants were included of IPD & OPD healthy controls with glycosylated hemoglobin levels under 6% were included. Blood samples, collected using sterile clot activator or plain vials, were stored at -20°C. The biomarker score that comprised significant differences in age, gender distribution, and metabolic indicators are seen between the diabetes (n=105) and control (n=105) groups. Increase in both Adiponectin and HbA1c% Mean±SD (6.86±0.23, p<0.0001; 22.71±2.01; p<0.0001) is indicative of deteriorating glycaemic control and an accompanying rise in inflammatory response. Positively correlate adiponectin levels with HbA1c levels (r2=0.398; p<0.0001), suggesting a link between inflammatory response and glucose control. Lower adiponectin levels are statistically associated with diabetes. Diabetes and adiponectin were negatively correlated and positive linear relationship between HbA1c and adiponectin levels. Adiponectin may be a significant factor useful in understanding the pathophysiology; they are likely to be straight forward instruments for predicting future risk of diabetes.

Mathematical model for assessing glycemic control in type 2 diabetes mellitus.

Glycated hemoglobin (HbA1c) and glycated albumin (GA) are vital markers for assessing glucose control in diabetes. This cross-sectional study involving 901 diagnosed type 2 diabetics aimed to compare calculated HbA1c, using the formula HbA1c = 2.6 + 0.03 x FBS (mg/dL), with directly measured HbA1c. Simultaneously, the study assessed the agreement between the two methods through regression analysis and explored correlations with various measures of glycemic control. The non-parametric Kolmogorov-Smirnov test indicated a non-normal data distribution, prompting appropriate statistical tests. Spearman's correlation coefficient revealed a strong correlation of calculated HbA1c, calculated GA, and estimated average glucose with measured parameters. Wilcoxon rank sum test indicated a significant difference between directly measured and calculated HbA1c (Z -9.487033, p < 0.0001). Passing Bablok regression analysis showed a significant deviation from linearity. Despite the potential cost benefits in resource-poor settings, caution is advised regarding interchangeable use of calculated and directly measured HbA1c in clinical decision-making. Data shows the importance of robust analytical methods in glycemic control assessment, offering insights for managing type 2 diabetes mellitus.

The role of glycosylation in non-productive adsorption of cellulase to lignin isolated from pretreated corn stover.

Glycosylation, a general post-translational modification for fungal cellulase, has been shown to affect cellulase binding to its substrate. However, the exact impact of glycosylation on cellulase-lignin interaction remain unclear. Here, we demonstrated that the lignin isolated from tetrahydrofuran-pretreated corn stover exhibits strong adsorption capability to cellulase due to its negatively charged and porous structure. For the cellulases with varying glycosylation levels, the less-glycosylated protein showed high adsorption capability to lignin, and that trend was observed for the main cellulase components secreted by Penicillium oxilicum, including endoglucanase PoCel5B, cellobiohydrolase PoCel7A-2, and ß-glucosidase PoBgl1. Additionally, N-glycan sites and motifs were examined using mass spectrometry, and protein structures with N-glycans were constructed, where PoBgl1 and PoCel7A-2 contained 13 and 1 glycosylated sites respectively. The results of molecular dynamics simulations indicated that the N-glycans impacted on the solvent-accessible surface area and secondary structure of protein, and the binding conformation of lignin fragment on cellulase, resulting in a decrease in binding energy (14 kcal/mol for PoBgl1 and 13 kcal/mol for PoCel7A-2), particularly for van der Waals and electrostatic interaction. Those findings suggested that glycosylation negatively impacted the lignin-cellulase interaction, providing a theoretical basis for the rational engineering of enzymes to reduce lignin-enzyme interaction.

The role of N-glycosylation in cancer.

Despite advances in understanding the development and progression of cancer in recent years, there remains a lack of comprehensive characterization of the cancer glycoproteome. Glycoproteins play an important role in medicine and are involved in various human disease conditions including cancer. Glycan-moieties participate in fundamental cancer processes like cell signaling, invasion, angiogenesis, and metastasis. Aberrant N-glycosylation significantly impacts cancer processes and targeted therapies in clinic. Therefore, understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and diagnosis. This review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells, including increased terminal sialylation, N-glycan branching, and core-fucosylation. Also, the role of N-glycosylation in tumor signaling pathways, migration, and metabolism are discussed. Glycoproteins and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been introduced. Collectively, understanding and exploring the cancer glycoproteome, along with its role in medicine, implication in cancer and other human diseases, highlights the significance of N-glycosylation in tumor processes, necessitating further research for potential anti-cancer targets and biomarkers.

Can artificial intelligence detect type 2 diabetes in women by evaluating the pectoral muscle on tomosynthesis: diagnostic study.

OBJECTIVES: This retrospective single-center analysis aimed to evaluate whether artificial intelligence can detect type 2 diabetes mellitus by evaluating the pectoral muscle on digital breast tomosynthesis (DBT). MATERIAL METHOD: An analysis of 11,594 DBT images of 287 consecutive female patients (mean age 60, range 40-77 years) was conducted using convolutional neural networks (EfficientNetB5). The inclusion criterion was left-sided screening images with unsuspicious interpretation who also had a current glycosylated hemoglobin A1c (HBA1c) % value. The exclusion criteria were inadequate imaging, history of breast cancer, and/or diabetes mellitus. HbA1c values between 5.6 and 6.4% were categorized as prediabetic, and those with values ≥ 6.5% were categorized as diabetic. A recorded HbA1c ≤ 5.5% served as the control group. Each group was divided into 3 subgroups according to age. Images were subjected to pattern analysis parameters then cropped and resized in a format to contain only pectoral muscle. The dataset was split into 85% for training and 15% for testing the model's performance. The accuracy rate and F1-score were selected as performance indicators. RESULTS: The training process was concluded in the 15th epoch, each comprising 1000 steps, with an accuracy rate of 92% and a loss of only 0.22. The average specificity and sensitivity for all 3 groups were 95%. The F1-score was 0.95. AUC-ROC was 0.995. PPV was 94%, and NPV was 98%. CONCLUSION: Our study presented a pioneering approach, applying deep learning for the detection of diabetes mellitus status in women using pectoral muscle images and was found to function with an accuracy rate of 92%. CRITICAL RELEVANCE STATEMENT: AI can differentiate pathological changes within pectoral muscle tissue by assessing radiological images and maybe a potential diagnostic tool for detecting diabetes mellitus and other diseases that affect muscle tissues. KEY POINTS: • AI may have an opportunistic use as a screening exam for diabetes during digital breast tomosynthesis. • This technique allows for early and non-invasive detection of diabetes mellitus by AI. • AI may have broad applications in detecting pathological changes within muscle tissue.

Early HbA1c Levels as a Predictor of Adverse Obstetric Outcomes: A Systematic Review and Meta-Analysis.

Background: The objective was to assess the association between early HbA1c levels and pregnancy complications and whether this relationship is affected when HbA1c thresholds are greater than or less than 39 mmol/mol (5.7%). Methods: Electronic searches of the MEDLINE and EMBASE databases up to October 2022 were conducted. We included retrospective and prospective observational studies. The inclusion criteria were as follows: HbA1c measurements taken at <20 weeks' gestation, singleton pregnancy, and no pre-existing diabetes mellitus. Results: We assessed the certainty of the evidence with the GRADE system. We determined the proportion of patients in each group who met the criteria for obstetrical outcomes and pooled data into two subgroups according to the HbA1c threshold: <39 mmol/mol or >39 mmol/mol (5.7%). Sixteen studies with a total of 43,627 women were included. An association between elevated early HbA1c levels and pre-eclampsia, large for gestational age (LGA), macrosomia, and preterm delivery (RR 2.02, 95% CI 1.53-2.66; RR 1.38, 95% CI 1.15-1.66; RR 1.40, 95% CI 1.07-1.83; and RR 1.67, 95% CI 1.39-2.0, respectively) was shown, with a moderate-high grade of certainty. According to the subgroup analysis of all studies, LGA, pre-eclampsia, and labour induction were associated with elevated HbA1c levels only in studies using an HbA1c threshold >39 mmol/mol (5.7%). The association between HbA1c levels and premature birth was statistically significant in studies using both higher and lower HbA1c thresholds. Conclusions: Women with high early HbA1c levels below the range of diabetes presented an increased risk of pregnancy complications such as macrosomia, LGA, and pre-eclampsia. An early HbA1c threshold of >39 mmol/mol (5.7%) showed the strongest association with pregnancy complications.

The glycosylated hemoglobin level and the severity of cardiovascular involvement in patients with the first episode of acute coronary syndrome.

Background: The current study was carried out aiming at investigating the relationship between glycosylated hemoglobin level and coronary atherosclerosis in patients with the first episode of acute coronary syndrome. Methods: This case-control study evaluated 450 patients with the first episode of acute coronary syndrome in Ayatollah Rouhani Hospital in Babol (Iran) from 2011 to 2018. Based on glycosylated hemoglobin, patients were divided into three groups of non-diabetic, pre-diabetic, and diabetic (n=150 in each group). Since SYNTAX score and Gensini score are employed to evaluate the extent of cardiovascular disease and predict CVD in patients with CAD over long-term follow-up, we calculated SYNTAX score and Gensini score based on angiographic results. Results: Concerning the factors related to the severity of cardiovascular involvement, the results revealed no significant difference between the diabetic and pre-diabetic groups in terms of the frequency of patients in terms of SYNTAX score, Gensini score, and the number of vessels involved (0.142 and 87, respectively, and P=0.102). However, this difference between the diabetic and non-diabetic groups, as well as between the pre-diabetic and non-diabetic groups was statistically significant (respectively for SYNTAX score, p< 0.001 and P=0.001; for Gensini score, P=0.013 and P=0.019; and for the number of vessels involved P=0.001and p<0.001). Conclusion: According to the findings of the current study, since there was no significant difference between diabetic and pre-diabetic patients in terms of the components indicating the severity of cardiovascular involvement, pre-diabetes itself may be associated with the severity of cardiovascular involvement as a predisposing factor.

Serum tumor markers expression (CA199, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus.

BACKGROUND: Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus (T2DM) is associated with the levels of serum tumor markers of the digestive tract, such as cancer antigen (CA)199. Therefore, tumor markers in T2DM are important. AIM: To evaluate the expression of serum tumor markers [CA199, CA242, and car-cinoembryonic antigen (CEA)] and the clinical implications of the expression in T2DM. METHODS: For this observational study conducted at Hefei BOE Hospital, China, we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020. Levels of fasting blood glucose (FBG), tumor markers (CA199, CEA, and CA242), glycosylated hemoglobin (HbA1c), etc. were measured and group index levels were compared. Moreover, FBG and HbA1c levels were correlated with tumor marker levels. Tumor markers were tested for diagnostic accuracy in patients with > 9% HbA1c using the receiver operating curve (ROC) curve. RESULTS: The T2DM group had high serum FBG, HbA1c, CA199, and CEA levels (P < 0.05). A comparative analysis of the two groups based on HbA1c levels (Group A: HbA1c ≤ 9%; Group B: HbA1c > 9%) revealed significant differences in CEA and CA199 levels (P < 0.05). The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809, respectively. CA199, CEA, and CA242 levels positively correlated with HbA1c (r = 0.308, 0.426, and 0.551, respectively) and FBG levels (r = 0.236, 0.231, and 0.298, respectively). CONCLUSION: As compared to controls, serum CEA and CA199 levels were higher in patients with T2DM. HbA1c and FBG levels correlated with CA199, CEA, and CA242 levels. Patients with poorly controlled blood sugar must be screened for tumor markers.

Characterisation of Modular Polyketide Synthases Designed to Make Pentaene Analogues of Amphotericin B.

Glycosylated polyene macrolides are important antifungal agents that are produced by many actinomycete species. Development of new polyenes may deliver improved antibiotics. Here, Streptomyces nodosus was genetically re-programmed to synthesise pentaene analogues of the heptaene amphotericin B. These pentaenes are of interest as surrogate substrates for enzymes catalysing unusual, late-stage biosynthetic modifications. The previous deletion of amphotericin polyketide synthase modules 5 and 6 generated S. nodosus M57, which produces an inactive pentaene. Here, the chain-terminating thioesterase was fused to module 16 to generate strain M57-16TE, in which cycles 5, 6, 17 and 18 are eliminated from the biosynthetic pathway. Another variant of M57 was obtained by replacing modules 15, 16 and 17 with a single 15-17 hybrid module. This gave strain M57-1517, in which cycles 5, 6, 15 and 16 are deleted. M57-16TE and M57-1517 gave reduced pentaene yields. Only M57-1517 delivered its predicted full-length pentaene macrolactone in low amounts. For both mutants, the major pentaenes were intermediates released from modules 10, 11 and 12. Longer pentaene chains were unstable. The novel pentaenes were not glycosylated and were not active against Candida albicans. However, random mutagenesis and screening may yet deliver new antifungal producers from the M57-16TE and M57-1517 strains.

Association between glycated hemoglobin and risk of all-cause mortality in community patients with type 2 diabetes: A prospective cohort study.

AIMS/INTRODUCTION: To analyze the association between HbA1c level and the risk of all-cause mortality in community patients with type 2 diabetes mellitus, and to provide a scientific basis for the management of type 2 diabetes mellitus in the community. MATERIALS AND METHODS: Based on a Zhejiang rural community type 2 diabetes mellitus cohort, a total of 10,310 patients with type 2 diabetes mellitus with complete baseline and follow-up data were selected. The Cox proportional hazards regression model and the restricted cubic spline model were used to evaluate the relationship between the HbA1c level and the risk of all-cause mortality. RESULTS: During a mean follow-up of 5.5 years, 971 patients died. With HbA1c levels of 6.5-7.0% as the reference, after adjusting for relevant confounding factors, the HR(95%CI) of all-cause mortality with HbA1c levels of <5.5%, 5.5-6.5%, 7.0-8.0%, 8.0-9.0%, and ≥9.0% were 1.53 (1.08-2.15), 0.97 (0.79-1.21), 1.14 (0.92-1.41), 1.44 (1.14-1.83), and 2.08 (1.68-2.58), respectively. The HbA1c level was associated with the risk of all-cause mortality in a "J-shaped" manner. The risk of all-cause mortality was lowest when the HbA1c was 6.5-7.0%, and increased significantly when the HbA1c was ≥ 8.0% and the HbA1c was < 5.5% (P < 0.05). The risk of all-cause death in the HbA1c 5.5-6.5% group and the 7.0-8.0% group was not significant compared with the reference group (P > 0.05). CONCLUSIONS: The HbA1c levels were associated with the risk of all-cause mortality in type 2 diabetes mellitus in a "J-shaped" manner, a too high or a too low HbA1c level could increase the risk of death. Attention should be paid to the individual evaluation of patients and the setting of appropriate glycemic control goals.

Chrysin bonded to ß-d-glucose tetraacetate enhances its protective effects against the neurotoxicity induced by aluminum in Swiss mice.

OBJECTIVES: To evaluate whether the glycosylation of chrysin (CHR) enhances its protective effects against aluminum-induced neurotoxicity. METHODS: To compare the antioxidant, anticholinesterase, and behavioral effects of CHR with its glycosylated form (CHR bonded to ß-d-glucose tetraacetate, denoted as LQFM280), we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (aluminum-induced neurotoxicity in Swiss mice) models. KEY FINDINGS: LQFM280 demonstrated higher antioxidant activity than CHR in both models. Specifically, LQFM280 exhibited the ability to exert antioxidant effects in the cytoplasm of SH-SY5Y cells, indicating its competence in traversing neuronal membranes. Remarkably, LQFM280 proved more effective than CHR in recovering memory loss and counteracting neuronal death in the aluminum chloride mice model, suggesting its increased bioavailability at the brain level. CONCLUSIONS: The glycosylation of CHR with ß-d-glucose tetraacetate amplifies its neuroprotective effects, positioning LQFM280 as a promising lead compound for safeguarding against neurodegenerative processes involving oxidative stress.

Associations of glycosylated hemoglobin, pre-diabetes, and type 2 diabetes with incident lung cancer: A large prospective cohort study.

BACKGROUND: The association of pre-diabetes and type 2 diabetes (T2D) with incident lung cancer is uncertain, and the incident risk across the glycemic spectrum is unclear. We aimed to explore the associations of glycosylated hemoglobin (HbA1c), pre-diabetes, and T2D with incident lung cancer in a large prospective cohort. METHODS: Leveraging a total of 210,779 cancer-free adults recruited in the UK Biobank between 2006 and 2010. We performed multivariable Cox proportional hazards models and restricted cubic spline methods to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of HbA1c, pre-diabetes, and T2D with incident lung cancer. RESULTS: During a median follow-up of 11.06 years, 1738 incident lung cancer cases were ascertained. The incidence of lung cancer was 20% higher among people with diabetes (HR: 1.20, 95% CI: 1.02 to 1.42) and 38% higher among people with pre-diabetes (HR: 1.38, 95% CI: 1.15 to 1.65). After dividing people with diabetes by whether taking antidiabetic medications, the incidence was 28% higher among people with diabetes without medications (HR: 1.28, 95% CI: 1.02 to 1.61) and 15% higher among people with diabetes with medications (HR: 1.15, 95% CI: 0.93 to 1.41). The increased risk of incident lung cancer for each standard deviation (6.45 mmol/mol) increase in HbA1c was more pronounced across HbA1c values of 32-42 mmol/mol (HR: 1.37, 95% CI: 1.18 to 1.59). The risk was more pronounced among participants <60 years. CONCLUSIONS: Pre-diabetes and T2D are associated with an increased incidence of lung cancer. The increased risk of incident lung cancer is more pronounced across HbA1c values of 32-42 mmol/mol, which are currently considered normal values.