Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Air and argon cold plasma effects on lipolytic enzymes inactivation, physicochemical properties and volatile profiles of lightly-milled rice.

This study investigated the effectiveness of cold-plasma treatment using air and argon as input gas on deactivation of lipolytic enzymes in lightly-milled-rice (LMR). The results showed no significant inactivation in lipase and lipoxygenase using air-plasma. However, using argon as input gas, the residual activities of lipase and lipoxygenase were reduced to 64.51 % and 29.15 % of initial levels, respectively. Argon plasma treatment resulted in more substantial augmentation in peak and breakdown viscosities of LMR starch, suggesting an enhancement in palatability of cooked LMR with increased stickiness and decreased hardness. In contrast to the decrease in volatile compounds in LMR following argon plasma treatment, the concentrations of several prevalent aroma compounds, including 1-hexanol, 1-hexanal, and 2-pentylfuran, exhibited significant increments, reaching 1489.70 ng/g, 3312.10 ng/g, and 58.80 ng/g, respectively. These findings suggest the potential for enhancing various facets of the commercial qualities of LMR by utilizing different input gases during plasma treatment.

Deep learning-based fundus image analysis for cardiovascular disease: a review.

It is well established that the retina provides insights beyond the eye. Through observation of retinal microvascular changes, studies have shown that the retina contains information related to cardiovascular disease. Despite the tremendous efforts toward reducing the effects of cardiovascular diseases, they remain a global challenge and a significant public health concern. Conventionally, predicting the risk of cardiovascular disease involves the assessment of preclinical features, risk factors, or biomarkers. However, they are associated with cost implications, and tests to acquire predictive parameters are invasive. Artificial intelligence systems, particularly deep learning (DL) methods applied to fundus images have been generating significant interest as an adjunct assessment tool with the potential of enhancing efforts to prevent cardiovascular disease mortality. Risk factors such as age, gender, smoking status, hypertension, and diabetes can be predicted from fundus images using DL applications with comparable performance to human beings. A clinical change to incorporate DL systems for the analysis of fundus images as an equally good test over more expensive and invasive procedures may require conducting prospective clinical trials to mitigate all the possible ethical challenges and medicolegal implications. This review presents current evidence regarding the use of DL applications on fundus images to predict cardiovascular disease.

Effects of Protein Components on the Chemical Composition and Sensory Properties of Millet Huangjiu (Chinese Millet Wine).

Millet Huangjiu is a national alcoholic beverage in China. The quality of Chinese millet Huangjiu is significantly influenced by the protein components in the raw materials of millet. Therefore, in this study, the impact of different protein components on the quality of millet Huangjiu was investigated by adding exogenous proteins glutelin and albumin either individually or in combination. The study commenced with the determination of the oenological parameters of different millet Huangjiu samples, followed by the assessment of free amino acids and organic acids. In addition, the volatile profiles of millet Huangjiu were characterized by employing HS-SPME-GC/MS. Finally, a sensory evaluation was conducted to evaluate the overall aroma profiles of millet Huangjiu. The results showed that adding glutelin significantly increased the contents of total soluble solids, amino acid nitrogen, and ethanol in millet Huangjiu by 32.2%, 41.5%, and 17.7%, respectively. Furthermore, the fortification of the fermentation substrate with glutelin protein was found to significantly enhance the umami (aspartic and glutamic acids) and sweet-tasting (alanine and proline) amino acids in the final product. Gas chromatography-quadrupole mass spectrometry coupled with multivariate statistical analysis revealed distinct impacts of protein composition on the volatile organic compound (VOC) profiles of millet Huangjiu. Excessive glutelin led to an over-accumulation of alcohol aroma, while the addition of albumin protein proved to be a viable approach for enhancing the ester and fruity fragrances. Sensory analysis suggested that the proper amount of protein fortification using a Glu + Alb combination could enhance the sensory attributes of millet Huangjiu while maintaining its unique flavor characteristics. These findings suggest that reasonable adjustment of the glutelin and albumin contents in millet could effectively regulate the chemical composition and improve the sensory quality of millet Huangjiu.

Emodin reverses resistance to gemcitabine in pancreatic cancer by suppressing stemness through regulation of the epithelial­mesenchymal transition.

The present study aimed to explore the effects and underlying mechanisms of emodin (Emo) on gemcitabine (GEM)-resistant pancreatic cancer. GEM-resistant SW1990 cells (SW1990/GZ) were established by successively doubling the concentration of GEM. Cell viability was measured using the CCK-8 assay and flow cytometry was used to measure cell apoptosis. Cell migration was assessed using a Transwell assay. Sphere and colony-formation assays were used to evaluate cell self-renewal. The expression levels of epithelial-mesenchymal transition (EMT) and stem cell biomarkers were determined using western blotting. Snail family transcriptional repressor 1 gene (Snail) was overexpressed by transfecting cells with pcDNA3.1-Snail plasmids. A xenograft model was established in nude mice by using SW1990/GZ and Snail-overexpressing SW1990/GZ cells. Proliferation, migration, self-renewal and EMT progression of GEM-treated SW1990/GZ cells were significantly suppressed in vitro by Emo treatment, whereas the overexpression of Snail abolished the aforementioned effects. In in vivo, the antitumor activity of GEM and the inhibitory effect of GEM against EMT progression and stem-like characteristics were enhanced by treatment with Emo, whilst overexpression of Snail reversed these effects. In conclusion, Emo reversed GEM resistance in pancreatic cancer by suppressing stemness and regulating EMT progression.

Application of Improved U-Net Convolutional Neural Network for Automatic Quantification of the Foveal Avascular Zone in Diabetic Macular Ischemia.

Objectives: The foveal avascular zone (FAZ) is a biomarker for quantifying diabetic macular ischemia (DMI), to automate the identification and quantification of the FAZ in DMI, using an improved U-Net convolutional neural network (CNN) and to establish a CNN model based on optical coherence tomography angiography (OCTA) images for the same purpose. Methods: The FAZ boundaries on the full-thickness retina of 6 × 6 mm en face OCTA images of DMI and normal eyes were manually marked. Seventy percent of OCTA images were used as the training set, and ten percent of these images were used as the validation set to train the improved U-Net CNN with two attention modules. Finally, twenty percent of the OCTA images were used as the test set to evaluate the accuracy of this model relative to that of the baseline U-Net model. This model was then applied to the public data set sFAZ to compare its effectiveness with existing models at identifying and quantifying the FAZ area. Results: This study included 110 OCTA images. The Dice score of the FAZ area predicted by the proposed method was 0.949, the Jaccard index was 0.912, and the area correlation coefficient was 0.996. The corresponding values for the baseline U-Net were 0.940, 0.898, and 0.995, respectively, and those based on the description data set sFAZ were 0.983, 0.968, and 0.950, respectively, which were better than those previously reported based on this data set. Conclusions: The improved U-Net CNN was more accurate at automatically measuring the FAZ area on the OCTA images than the traditional CNN. The present model may measure the DMI index more accurately, thereby assisting in the diagnosis and prognosis of retinal vascular diseases such as diabetic retinopathy.

Genetically Predicted Circulating Omega-3 Fatty Acids Levels Are Causally Associated With Increased Risk for Systemic Lupus Erythematosus.

BACKGROUND: Accumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive. OBJECTIVES: This study was conducted to evaluate the causal relationships between omega-3/omega-6 PUFAs and SLE by performing the Mendelian randomization (MR) analysis. METHODS: Genome-wide significant single-nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) of circulating omega-3/omega-6 levels (n = up to 13,544) and GWAS meta-analyses of SLE (n = 14,267), respectively. The bidirectional two-sample MR (TSMR) analysis was conducted to infer the causality. RESULTS: The inverse-variance weighted (IVW) method revealed that genetically determined per SD increase in omega-3 levels were causally associated with an increased risk for SLE (odds ratios [ORs] = 1.49, 95% CI: 1.07, 2.08, p = 0.021), but no causal effect of omega-6 on the risk SLE was observed (IVW OR = 1.06, 95% CI: 0.72, 1.57, p = 0.759). In addition, there were no significantly causal associations in genetic predisposition to SLE with the changes of omega-3 and omega-6 levels, respectively (IVW beta for omega-3: 0.007, 95% CI: -0.006, 0.022, p = 0.299; IVW beta for omega-6: -0.008, 95% CI: -0.023, 0.006, p = 0.255). CONCLUSION: The present study revealed the possible causal role of omega-3 on increasing the risk for SLE, it could be the potential implications for dietary recommendations.

Positive circumferential resection margin in locally advanced esophageal cancer: an updated systematic review and meta-analysis.

BACKGROUND: The impact of positive circumferential resection margin on prognosis in esophageal cancer is under controversy. Previous systematic reviews and meta-analyses had limitations. This updated systematic review and meta-analysis aimed to assess the prognostic impact of positive circumferential resection margin in esophageal cancer.PubMed and Web of Science were searched for studies investigating the association between circumferential resection margin status and prognosis in esophageal cancer. Study population were focused on T3 and/or T4a patients. Study selection was based on availability of survival information (Kaplan-Meier curves and adjusted analysis). Random-effects models were used to summarize hazard ratios for overall survival and disease-free survival.According to College of American Pathologists criteria, circumferential resection margin-positive patients had shorter median overall survival (P < 0.0001) and shorter median disease-free survival (P < 0.0001) compared with circumferential resection margin-negative patients. The pooled hazard ratios for overall survival and disease-free survival were 2.06 (95% confidence interval, 1.68-2.53; P < 0.0001) and 2.00 (95% confidence interval, 1.41-2.84; P < 0.0001), respectively. According to the Royal College of Pathologists criteria, circumferential resection margin-positive patients had shorter median overall survival (P < 0.0001) and shorter median disease-free survival (P < 0.0001) compared with circumferential resection margin-negative patients. The pooled hazard ratios for overall survival and disease-free survival were 1.31 (95% confidence interval, 1.16-1.48; P < 0.0001) and 1.31 (95% confidence interval, 1.09-1.57; P < 0.0001), respectively.ompared with negative circumferential resection margin, positive circumferential resection margin is associated with worse survival outcomes in esophageal cancer.

Developing and predicting of early mortality after endovascular thrombectomy in patients with acute ischemic stroke.

Background: Stroke is one of the leading causes of mortality across the world. However, there is a paucity of information regarding mortality rates and associated risk factors in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). In this study, we aimed to clarify these issues and analyzed previous publications related to mortality in patients treated with EVT. Methods: We analyzed the survival of 245 consecutive patients treated with mechanical thrombectomy for AIS for which mortality information was obtained. Early mortality was defined as death occurring during hospitalization after EVT or within 7 days following hospital discharge from the stroke event. Results: Early mortality occurred in 22.8% of cases in this cohort. Recanalization status (modified thrombolysis in cerebral infarction, mTICI) (p = 0.002), National Institute of Health Stroke Scale Score (NIHSS) score 24-h after EVT (p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (p < 0.001) were independently associated with early mortality. Age, sex, cardiovascular risk factors, NIHSS score pre-treatment, Alberta Stroke Program Early CT Score (ASPECTS), stroke subtype, site of arterial occlusion and timing form onset to recanalization did not have an independent influence on survival. Non-survivors had a shorter hospitalization (p < 0.001) but higher costs related to their hospitalization and outpatient care. Conclusion: The recanalization status, NIHSS score 24-h after EVT and sICH were predictors of early mortality in AIS patients treated with EVT.

Therapeutic Potential of Galectin-1 and Galectin-3 in Autoimmune Diseases.

Galectins are a highly conserved protein family that binds to ß-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. They can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies have indicated that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. This information may provide a novel and promising therapeutic target for autoimmune diseases.

Elevated Circulating Thrombomodulin Levels in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

OBJECTIVES: Thrombomodulin (TM) is closely related to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). However, current evidence on circulating TM levels in SLE patients is contradictory. We conducted this meta-analysis to more accurately assess circulating TM levels in patients with SLE and lupus nephritis (LN) and to analyze related influencing factors. METHODS: Systematic search of relevant documents was conducted in PubMed, Embase, and The Cochrane Library databases (up to 28 February 2021). Studies on the comparison of circulating TM between SLE patients and controls were screened and evaluated for inclusion. Random-effects model analysis was applied to calculate the combined standardized mean difference (SMD) with a 95% confidence interval (CI). Heterogeneity was estimated by Q statistics and I2. RESULTS: A total of 353 articles were identified, 14 provided adequate information for this study finally. The results illustrated that SLE patients had higher TM levels than healthy controls (SMD=0.38, 95% CI: 0.02 to 0.74, p=0.04). Circulating TM levels were increased in patients with active SLE compared to inactive SLE patients (SMD=1.12, 95% CI: 0.03 to 2.20, p=0.04). In addition, circulating TM levels of SLE patients with LN were higher than those without LN (SMD=4.55, 95% CI: 1.97 to 7.12, p=0.001). CONCLUSION: The circulating TM levels in SLE patients are enhanced. In addition, circulating TM levels may be practical in reflecting the disease activity and nephritis involvement of SLE patients.

Integrated Analysis of Metabolome and Volatile Profiles of Germinated Brown Rice from the Japonica and Indica Subspecies.

In the present study, germinated brown rice (GBR) from three Japonica and three Indica rice cultivars were subjected to metabolomics analysis and volatile profiling. The statistical assessment and pathway analysis of the metabolomics data demonstrated that in spite of significant metabolic changes in response to the germination treatment, the Japonica rice cultivars consistently expressed higher levels of several health-promoting compounds, such as essential amino acids and γ-aminobutyric acid (GABA), than the Indica cultivars. No clear discriminations of the volatile profiles were observed in light of the subspecies, and the concentrations of the volatile organic compounds (VOCs), including alkenes, aldehydes, furans, ketones, and alcohols, all exhibited significant reductions ranging from 26.8% to 64.1% after the germination. The results suggest that the Japonica cultivars might be desirable as the raw materials for generating and selecting GBR food products for health-conscious consumers.

Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.

Design and Initial Validation of a Humanistic Care Evaluation Tool.

OBJECTIVE: This study aimed at developing and validating a humanistic care tool in Anhui province that could be used across Chinese public hospitals, and to reflect the humanistic care from patients' perspective. PARTICIPANTS: A cross-sectional survey was conducted in three public hospitals of Anhui Province, China by adopting simple random sampling, which included 312 outpatients and 323 inpatients. METHODS: The dimensions of the tool were set according to "Further Improve Medical Service Action Plan" in China and Patient-Doctor Relationship Questionnaire. Cronbach's alpha values were calculated and used to evaluate the reliability of this tool. Construct validity was tested by the exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The associations between characteristics and humanistic care were analyzed by binary logistic regression. RESULTS: These initial findings showed that about two-thirds of the respondents experienced humanistic care. Both the reliability and construct validity of the humanistic care evaluation tool were suitable Social aspects (location and yearly income), treatment style and having a regular doctor were significantly associated with better humanistic care (all P<0.05). CONCLUSION: The humanistic care tool can directly reflect the humanistic care from patients' perspective, and can be popularized and applied across Chinese public hospitals. These findings have important implications to further improve medical service in Chinese public hospitals.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Circadian clock genes as promising therapeutic targets for autoimmune diseases.

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.

Association between ambient air pollution and tuberculosis risk: A systematic review and meta-analysis.

There is a growing body of evidence suggesting an association between air pollution exposure and tuberculosis (TB) incidence, but no meta-analysis has assembled all evidence so far. This review and meta-analysis aimed to derive a more reliable estimation on the association between air pollution and TB incidence. PubMed, Embase and Web of Science electronic databases were systemically searched for eligible literature. The PECO framework was used to form the eligibility criteria. Effect estimates and 95% confidence intervals (CIs) published in the included studies were pooled quantitatively. Seventeen articles met the inclusion criteria. The pooled estimates showed that long-term exposure to particulate matter with an aerodynamic diameter ≤10 µm (PM10) was associated with increased incidence of TB (per 10 µg/m3 increase in concentrations of PM10: risk ratios (RR) = 1.058, 95% CI: 1.021-1.095). Besides, long-term exposure to sulfur dioxide (SO2) and nitrogen dioxide (NO2) were significantly associated with TB incidence (per 1 ppb increase, SO2: RR = 1.016, 95% CI: 1.001-1.031; NO2: 1.010, 95% CI: 1.002-1.017). We did not find a significant association of PM2.5, ozone (O3) or carbon monoxide (CO) with TB risk, regardless of long-term or short-term exposure. However, in view of the 2016 ASA Statement and the biological plausibility of PM2.5 damaging host immunity, the association between PM2.5 and TB risk remains to be further established. This meta-analysis shows that long-term exposure to PM10, SO2 or NO2 is associated with increased odds of TB, and the specific biological mechanisms warrant further research.

Effects of PI3K/AKT/mTOR pathway regulation of HIF-1α on Lanthanum-induced neurotoxicity in rats.

This study examined the effects of the AKT/mTOR/HIF-1α signaling pathway on learning and memory in offspring rats induced by lanthanum from neuroethology and molecular biology perspectives. 32 pregnant adult Wistar rats were divided into four groups randomly: control group (NC), 0.25%, 0.5% and 1.0% LaCl3 groups (n = 8). All rats were poisoned through free drinking from day 0 of pregnancy to postnatal day 21 (suckling period). All offspring rats were poisoned through free drinking from delactation to postnatal day 48. Offspring rats aged 49-days-old were used as sampling objects to construct an LaCl3 poisoning model of offspring rats. Changes in hippocampal neurons, apoptosis of hippocampal neurons, learning and memory abilities of LaCl3-poisoned animals were measured by Nissl staining, TUNEL method and the shuttle box test, respectively. Expressions of PI3K, AKT, and mTOR, HIF-1α, and VEGF in the hippocampus were tested by qPCR and Western blot. Distributions of PI3K and p-AKT in hippocampal neurons were observed through the immunohistochemical method. With increasing LaCl3 dose, lightning strike time and active avoidance incubation period of offspring rats in the different LaCl3 groups were significantly prolonged. The Nissl body positive neurons of hippocampal neurons gradually declined while apoptosis in cells increased. The expressions of both mRNA (PI3K, AKT, mTOR, HIF-1α, VEGF) and proteins (PI3K, p-AKT, p-mTOR, HIF-1α, VEGF) in the hippocampus of the LaCl3 groups were significantly lower than those of NC group (p < 0.05). LaCl3 poisoning can induce developmental injuries in hippocampal neurons and can increase cell apoptosis. As a result, learning and memory abilities of offspring rats, as well as the expressions of PI3K/AKT/mTOR, are decreased, thus inhibiting activation of HIF-1α and influencing the expression of the downstream VEGF gene.

A highly sensitive detection of carbendazim pesticide in food based on the upconversion-MnO2 luminescent resonance energy transfer biosensor.

Carbendazim (CBZ) pesticide residues in food products have become a growing concern in recent years. Herein, a sensitive biosensor for detecting CBZ was developed based on luminescent resonance energy transfer (LRET) from aptamer labeled upconversion nanoparticles (UCNPs, donor) to manganese dioxide (MnO2, acceptor) nanosheets. The strong overlap between the absorption spectrum of MnO2 and the UCNPs fluorescence emission allowed the luminescence quenching. With the addition of CBZ, it tended to bind with specific aptamers, which culminated in the UCNPs-aptamer dropping off MnO2 nanosheets and restoring the fluorescence. A linear calibration plot between logarithmic CBZ concentration and fluorescence intensity was acquired in the range of 0.1-5000 ng·mL-1, with a limit of detection 0.05 ng·mL-1, indicating that the UCNPs- MnO2 aptasensor is a rapid, sensitive and specific quantitative detection platform for CBZ. Furthermore, the precision and accuracy of the developed LRET biosensor was validated by HPLC method with no significant differences.

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

The circadian clock plays a crucial role in the progress of systemic lupus erythematosus (SLE). In this study, we performed a case-control study to explore the association between Period 2 (PER2) gene single nucleotide polymorphisms (SNPs) and the susceptibility of systemic lupus erythematosus (SLE). A total of 492 SLE patients and 493 healthy controls were included. The improved multiple ligase detection reaction (iMLDR) was used for genotyping. The correlations between four SNPs of PER2 (rs10929273, rs11894491, rs36124720, rs934945) and the genetic susceptibility and clinical manifestations of SLE were analyzed. Significant differences were observed in the distributions of allele frequencies and genotype under dominant model in rs11894491 between SLE patients and controls (p = 0.030, p = 022, respectively). We hypothesized that PER2 gene SNPs was related to the genetic susceptibility and clinical manifestations, implying the potential role of PER2 in the pathogenesis of SLE.