Recent advances in optical biosensing and imaging of telomerase activity and relevant signal amplification strategies.

Telomerase as a new valuable biomarker for early diagnosis and prognosis evaluation of cancer has attracted much interest in the field of biosensors, cell imaging, and drug screening. In this review, we mainly focus on different optical techniques and various signal amplification strategies for telomerase activity determination. Fluorometric, colorimetry, chemiluminescence, surface-enhanced Raman scattering (SERS), and dual-mode techniques for telomerase sensing and imaging are summarized. Signal amplification strategies include two categories: one is nucleic acid-based amplification, such as rolling circle amplification (RCA), the hybridization chain reaction (HCR), and catalytic hairpin assembly (CHA); the other is nanomaterial-assisted amplification, including metal nanoclusters, quantum dots, transition metal compounds, graphene oxide, and DNA nanomaterials. Challenges and prospects are also discussed to provide new insights for future development of multifunctional strategies and techniques for in situ and in vivo analysis of biomarkers for accurate cancer diagnosis.

No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Correlation of weight-adjusted waist index with diabetic retinopathy in US adults aged ≥ 40 years: the NHANES 2005-2008.

The effect of obesity on diabetic retinopathy (DR) has been under scrutiny in recent years. The weight-adjusted waist index (WWI) has been reported to better assess the degree of centripetal obesity in humans, with a higher WWI indicating a higher amount of body fat. The present study is the first to investigate the relationship between WWI and DR and to assess the difference in the predictive ability of WWI and other obesity indices for DR. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Researchers collected complete anthropometric data (weight and waist circumference), dilated fundus images, and adult baseline information. Independent interactions between WWI and DR were investigated using multivariate regression and subgroup analyses. In addition, nonlinear associations and threshold effects between WWI and DR were searched for by smoothed curve fitting and by two-stage linear regression modeling. Finally, the receiver operating characteristic curve (ROC) was plotted to compare the predictive power of WWI with other indices of obesity for DR. A total of 1228 eligible patients with diabetes were collected in this study. There were 631 (51.38%) males and 597 (48.62%) females. Among them, 545 (44.38%) were without diabetic retinopathy, 555 (45.20%) had mild diabetic retinopathy, 100 (8.14%) had moderate/severe diabetic retinopathy and 28 (2.28%) had proliferative diabetic retinopathy (PDR). In the fully adjusted model, each unit increase in WWI was associated with a corresponding 31% reduction in the prevalence of DR [OR (95% CI) = 0.69 (0.58, 0.83)]. Compared with subjects in the lowest quartile (quartile 1), subjects in the highest quartile of WWI levels (quartile 4) were 45% less likely to have DR [OR (95% CI) = 0.55 (0.38, 0.78)]. In the case of female participants, a U-shaped correlation was observed between WWI and DR with an inflection point of 11.49. WWI also possesses a better predictive ability for DR compared to obesity indicators such as weight, BMI, and ABSI. This study showed a negative association between WWI and DR in the U.S. population aged 40 years and older.

Association between Glycosylated Hemoglobin and Serum Uric Acid: A US NHANES 2011-2020.

Background: Serum uric acid (SUA) and glycosylated hemoglobin (HbA1c) were closely related to the body's metabolism. This study aimed to investigate the relationship between HbA1c and SUA in adults. Methods: This study selected 7293 participants aged ≥20 from 2011 to 2020 in the National Health and Nutrition Examination Survey (NHANES). The multivariate linear regression model was used to test the association between HbA1c and SUA. Subgroup analysis was performed according to age, gender, race, and body mass index (BMI). This study solved the relationship between HbA1c and SUA by fitting a smooth curve. Finally, the inflection point in the nonlinear relationship was calculated by the recursive algorithm, and the relationship between HbA1c and SUA on both sides of the inflection point was analyzed by the two-segment piecewise linear regression model. Results: All 7293 participants found a negative correlation between HbA1c and SUA by completely adjusting the model (ß = -7.93 and 95% CI: -9.49--6.37). In addition, when this study was stratified by gender, age, race, and BMI status, this negative correlation was still statistically significant. In the subgroup analysis, we found that the relationship between the two had different results due to gender differences. In men, HbA1c had a significant negative correlation with SUA. However, in women, the HbA1c value was positively correlated with SUA before 6.8%, and the HbA1c value was negatively correlated with SUA after 6.8%, which indicates that the relationship between HbA1c and SUA in women has changed in prediabetes and diabetes. Conclusion: This study shows that HbA1c is positively correlated with SUA in American adults before 7%. There is a negative correlation after the HbA1c value of 7%.

A convenient smartphone-assisted colorimetric for 6-Mercaptopurine detection using enhanced oxidase-like activity of ß-cyclodextrin modified MnO2 nanosheets.

6-mercaptopurine (6-MP) is widely used in the treatment of many diseases, but exhibits some serious side effects due to its toxicity. Therefore, it is important and imperative to effectively control and monitoring concentration of 6-MP. Herein, we designed a smartphone-assisted colorimetric sensing platform for 6-MP detection, based on an excellent ß-cyclodextrin modified MnO2 nanosheets (ß-CD@MnO2 NNS) mediated oxidase-like activity. ß-CD@MnO2 NNS can directly oxidizes 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB with color changes, yielding more than 3-fold higher oxidase-like catalytic activity compared with individual MnO2 NNS. After adding 6-MP, ß-CD@MnO2 NNS can be reduced to Mn2+ and lose their oxidase-like properties, resulting in a color and absorbance change for sensitive and selectivity detection of 6-MP. Meanwhile, the smartphone-based color recognition application can intuitively and simply measure the concentration of 6-MP. The limits of detection UV-vis instrument and smartphone were 0.35 µM and 0.86 µM, respectively. This method has also been successfully applied to the detection of real samples. Finally, this study provides a new promising platform for detection of 6-MP and is expected to be used in application of pharmaceutical analysis and biomedicine.

Bioinformatics study of the potential therapeutic effects of ginsenoside Rh3 in reversing insulin resistance.

Background: In recent years, the incidence of insulin resistance is increasing, and it can cause a variety of Metabolic syndrome. Ginsenosides have been clinically proven to improve fat metabolism and reduce insulin resistance, but their components and mechanism of action are still unclear. Objective: Ginsenoside, a bioactive compound derived from ginseng, exhibits significant potential in treating obesity, diabetes, and metabolic disorders. Despite evidence supporting its efficacy in ameliorating insulin resistance (IR) in obesity, the specific bioactive components and underlying mechanisms remain obscure. In this study, we endeavored to elucidate the potential molecular targets and pathways influenced by ginsenoside Rh3 (GRh3) to ameliorate IR in liver tissue. We employed a comprehensive approach that integrates system pharmacology and bioinformatics analysis. Materials and methods: Our methodology involved the identification of candidate targets for GRh3 and the profiling of differentially expressed genes (DEGs) related to IR in individuals with insulin resistance. The coalescence of candidate targets and DEGs facilitated the construction of a "GRh3-targets-disease" network for each tissue type, ultimately yielding 38 shared target genes. Subsequently, we conducted pathway enrichment analysis, established protein-protein interaction (PPI) networks, and identified hub targets among the GRh3 targets and IR-related DEGs. Additionally, we conducted animal experiments to corroborate the role of these hub targets in the context of GRh3. Results: Our investigation identified a total of 38 overlapping targets as potential candidates. Notably, our analysis revealed crucial hub targets such as EGFR, SRC, ESR1, MAPK1, and CASP3, alongside implicated signaling pathways, including those related to insulin resistance, the FoxO signaling pathway, the PPAR signaling pathway, and the IL-17 signaling pathway. This study establishes a robust foundation for the mechanisms underlying GRh3's efficacy in mitigating IR. Furthermore, these results suggest that GRh3 may serve as a representative compound within the ginsenoside family. Conclusion: This study elucidates the potential molecular targets and associated pathways through which GRh3 ameliorates IR, showcasing its multifaceted nature, spanning multiple targets, pathways, and mechanisms. These findings establish a robust foundation for subsequent experimental inquiries and clinical applications.

Optimization of an in vitro Pseudomonas aeruginosa Biofilm Model to Examine Antibiotic Pharmacodynamics at the Air-Liquid Interface.

Pseudomonas aeruginosa is an important cause of lower respiratory tract infections, such as ventilator-associated bacterial pneumonia (VABP). Using inhaled antibiotics to treat VABP can achieve high drug concentrations at the infection site while minimizing systemic toxicities. Despite the theoretical advantages, clinical trials have failed to show a benefit for inhaled antibiotic therapy in treating VABP. A potential reason for this discordance is the presence of biofilm-embedded bacteria in lower respiratory tract infections. Drug selection and dosing are often based on data from bacteria grown planktonically. In the present study, an in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model was optimized to evaluate the activity of simulated epithelial lining fluid exposures of inhaled and intravenous doses of polymyxin B and tobramycin against two P. aeruginosa strains. Antibiotic activity was also determined against the P. aeruginosa strains grown planktonically. Our study revealed that inhaled antibiotic exposures were more active than their intravenous counterparts across biofilm and planktonic populations. Inhaled exposures of polymyxin B and tobramycin exhibited comparable activity against planktonic P. aeruginosa. Although inhaled polymyxin B exposures were initially more active against P. aeruginosa biofilms (through 6 h), tobramycin was more active by the end of the experiment (48 h). Together, these data slightly favor the use of inhaled tobramycin for VABP caused by biofilm-forming P. aeruginosa that are not resistant to either antibiotic. The optimized in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model may be beneficial for the development of novel anti-biofilm agents or to optimize antibiotic dosing for infections such as VABP.

Determination of dimethylated nucleosides in serum from colorectal cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

RNA modifications play a crucial regulatory role in a variety of biological processes and are closely related to numerous diseases, including cancer. The diversity of metabolites in serum makes it a favored biofluid for biomarkers discovery. In this work, a robust and accurate hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach was established for simultaneous determination of dimethylated nucleosides in human serum. Using the established method, we were able to accurately quantify the concentrations of N6-2'-O-dimethyladenosine (m6Am), N2,N2-dimethylguanosine (m2,2G), and 5,2'-O-dimethyluridine (m5Um) in serum samples from 53 healthy controls, 57 advanced colorectal adenoma patients, and 39 colorectal cancer (CRC) patients. The results showed that, compared with healthy controls and advanced colorectal adenoma patients, the concentrations of m6Am and m2,2G were increased in CRC patients, while the concentration of m5Um was decreased in CRC patients. These results indicate that these three dimethylated nucleosides could be potential biomarkers for early detection of colorectal cancer. Interestingly, the level of m5Um was gradually decreased from healthy controls to advanced colorectal adenoma patients to CRC patients, indicating m5Um could also be used to evaluate the level of malignancy of colorectal tumor. In addition, this study will contribute to the investigation on the regulatory mechanisms of RNA dimethylation in the onset and development of colorectal cancer.

Study on the Buffering Effect of Physical Exercise on College Students' Psychological Stress / Estudio sobre el efecto amortiguador del ejercicio físico sobre el estrés psicológico de los estudiantes universitarios

In the face of stressful events beyond their own coping scope or negative evaluation, individuals will experience pressure and negative emotions will increase. Therefore, it is a very important research topic to adopt effective ways to adjust college students to correctly face psychological pressure and negative emotions, so as to promote their physical and mental health. Studies have shown that physical exercise, as a way of regulation, can promote mental health and individual mood. Most of the previous studies adopted transverse studies, and the follow-up studies were relatively limited, ignoring the changes at the individual level. A research method is designed to study the buffering effect of physical exercise on psychological stress of college students. To begin, study objectives and techniques are chosen, and descriptive statistics are computed. Second, the correlation coefficients of psychological pressure, negative mood, and physical activity among college students are compared and studied to complete the buffer effect research. The application value of the cushioning effect research technique is shown by the practical example analysis, which indicates that it can properly represent the cushioning impact of physical exercise on college students' psychological strain.(AU)