ASSOCIATION OF DIABETIC MACULAR EDEMA WITH QUALITY OF LIFE IN PATIENTS WITH TYPE 2 DIABETES: The Fushun Diabetic Retinopathy Cohort Study.

PURPOSE: To report the vision-related quality of life in patients with diabetic macular edema (DME) in a population-based study. METHODS: In this cross-sectional study, we analyzed 1,659 subjects with type 2 diabetes. Questionnaires were administered to assess the patient's vision-related quality of life. Diabetic macular edema severity was graded according to the established protocols. A subject's DME score ranged from 1 (no DME in either eye) to 7 (severe bilateral DME) using predefined criteria. RESULTS: Composite 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores for participants with DME were 88.9 (interquartile range [IQR]: 76.2-94.9) compared with 92.0 (IQR: 82.7-96.0) for those without DME ( P < 0.001). Locally weighted scatterplot smoothing plots depicted a consistent decline in composite NEI-VFQ-25 scores corresponding to the escalation of bilateral DME severity: starting from 88.59 for no DME in either eye, progressing through 86.65, 85.83, 85.31, 84.91, 83.85, and culminating at 82.71 for bilateral severe DME. Notably, the locally weighted scatterplot smoothing plots highlighted significant NEI-VFQ-25 composite score reduction at unilateral mild DME (slope m = -1.94). CONCLUSION: Significant changes in vision-related quality of life manifest in the early stage of DME. Therefore, early identification and intervention for these patients are crucial clinical objectives.

Construction of a novel prognostic model in skin cutaneous melanoma based on chemokines-related gene signature.

Skin cutaneous melanoma, SKCM, is one of the most aggressive treatment-resistant tumours. Despite the fact that the BRAF oncogene and immunological checkpoints such as PD-1/PD-L1 and CTLA-4 have enhanced the therapeutic efficacy of SKCM, the subsequent resistance mechanisms and remedies have raised concerns. Chemokines have a significant role in the immunological milieu of tumor, which may increase the efficacy of checkpoint blockade and serve as a possible therapeutic intervention route. However, there is still no chemokine-based typing and risk model to provide a prognosis and therapeutic efficacy assessment for SKCM patients. In this study, we verified the distinct differences of prognostic stratification as well as immune characteristics between two chemokine-related clusters in SKCM patients. Two clusters of DEGs were discovered to be primarily enriched in B and T cell receptor signaling pathways as well as TNF signaling via NF-kappa-B. Based on 14 prognosis-related DEGs from aforementioned two clusters (CCL8, GBP2, GBP4, SRNG, HLA-DMB, RARRES3, HLA-DQA1, PARP12, APOL3, IRF1, HLA-DRA, UBE2L6, IL2RA and CD38), a chemokine-related 14-gene prognostic model was established. At the same time, researchers explored differences between the low-risk and high-risk groups in clinical traits, the proportion of infiltration of 22 different types of immune cells, and how well medications worked. The risk score model's immunotherapy and prognostic predictions were also confirmed in testing groups. Based on the finding, we can claim that there is a clear link between chemokines and TME in SKCM. The risk score may perform as a trustworthy prediction model, giving therapeutic benefits for both chemotherapy and immunotherapy, as well as being beneficial for clinical decision making in SKCM patients.

Pan-cancer investigation of psoriasis-related BUB1B gene: genetical alteration and oncogenic immunology.

Unknown factors contribute to psoriasis' hyperproliferative, chronic, inflammatory, and arthritic features. Psoriasis patients have been linked to an increased risk of cancer, though the underlying genetics remain unknown. Since our prior research indicated that BUB1B contributes to the development of psoriasis, we designed and carried out this investigation using bioinformatics analysis. Using the TCGA database, we investigated the oncogenic function of BUB1B in 33 tumor types. To sum up, our work sheds light on BUB1B's function in pan-cancer from various perspectives, including its pertinent signaling pathways, mutation locations, and connection to immune cell infiltration. BUB1B was shown to have a non-negligible role in pan-cancer, which is connected to immunology, cancer stemness, and genetic alterations in a variety of cancer types. BUB1B is highly expressed in a variety of cancers and may serve as a prognostic marker. This study is anticipated to offer molecular details on the elevated cancer risk that psoriasis sufferers experience.

Pan-Cancer Analysis of BUB1B/hsa-miR-130a-3p Axis and Identification of Circulating hsa-miR-130a-3p as a Potential Biomarker for Cancer Risk Assessment.

Based on the fact that very little was found in the literature on the question of potential molecules and mechanism for high risk of cancer in patients with psoriasis, this study was designed and performed based on bioinformatics analysis including WGCNA. The most striking result to emerge from the data is that BUB1B/hsa-miR-130a-3p axis, closely related to the development of psoriasis, also plays a remarkable role in multiple cancer development. The expression patterns of hsa-miR-130a-3p were found significantly changed in multiple tumors, which was also associated with prognosis. Additionally, hsa-miR-130a-3p was downregulated in lesion skin of psoriasis, but there was no difference in blood between psoriasis patients and normal controls. Circulating has-miR-130a-3p was found to have a higher level of blood in multiple tumor patients, suggesting that hsa-miR-130a-3p has the potential to be a blood biomarker for cancer risk assessment in patients with psoriasis.

An integrative analysis to reveal that CLEC2B and ferroptosis may bridge the gap between psoriatic arthritis and cancer development.

Patients with cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) are reported with increased cancer risk, but the underlying mechanism is less clear, especially the association between the presence of PsA and cancer risk. Motivated by the role of ferroptosis in the progression of cancers as well as inflammation response in psoriasis, this experiment attempts to investigate the relationship between ferroptosis regulators and hub genes in PsA by bioinformatic analysis. The findings revealed an exclusive correlation between CISD1 (ferroptosis regulator) and CLEC2B (hub gene) in PsA group as well as multiple cancer types. Furthermore, CLEC2B was discovered differentially expressed in a variety of cancers and is closely associated with immune cell infiltration as well as immune checkpoints. These results indicate that ferroptosis may act as a bridge between psoriatic arthritis and the onset of certain malignancies.

Injectable and Biodegradable Chitosan Hydrogel-Based Drug Depot Contributes to Synergistic Treatment of Tumors.

Combined therapy provides a more effective method in the treatment of tumors and becomes a research hotspot. To improve treatment outcomes and reduce serious side effects, hydrogel-based local delivery was developed herein to form a drug depot in suit to eliminate tumors. Indocyanine green and imiquimod were coencapsulated in the novel temperature-sensitive chitosan hydrogel. After intratumoral injection of the hydrogel, indocyanine green that accumulated in the tumor area could induce thermal ablation of primary tumors under laser irradiation. In the presence of imiquimod, the immune effects increased the probability of complete ablation of primary tumors and inhibition of metastases. Combined with cyclophosphamide, the enhanced immunological responses would further inhibit tumors and prolong the survival time. In a word, this work offered an excellent local delivery platform that enabled a remarkable combined antitumor strategy and achieved synergistic therapeutic effects.

Topography effect on Aspergillus flavus occurrence and aflatoxin B1 contamination associated with peanut.

Aflatoxin B1 is a strong carcinogenic and toxic fungal toxin produced by Aspergillus flavus and other Aspergillus species, and can seriously threaten the health of consumers and the safety and quality of agricultural products. Aspergillus in agricultural products are closely related to topography and symbiotic microbes. It is not fully clear that how topography affects the assembly process of A. flavus and symbiotic fungi on plant. In this study, we analyzed the structure and assembly process of fungi on the peanut. We also performed the metatranscriptome analysis, identified the functional genes and metabolic pathways enriched in both A. flavus and its symbiotic fungi. In our experiment, terrain and soil properties could significantly affect the gene expression of microbiome, A. flavus abundance and infection ability to peanuts. Meanwhile, the Permanova correlation analysis revealed that differentially expressed genes were strongly correlated with the soil physicochemical factors. Furthermore, metabolomic analysis identified the main metabolites associated with A. flavus and aflatoxin B1, the results proved that the terrain significantly affected the microorganisms associated with peanut pods to produce a variety of metabolites. In conclusion, our results indicate that topography can significantly influence the assembly process of A. flavus and microorganisms, the activation of functional genes and metabolic pathways, the enrichment of aflatoxin-producing fungi.

Role of mean platelet volume in differential diagnosis of adult-onset Still's disease and sepsis

SUMMARY OBJECTIVES: Mean platelet volume is a simple biomarker for inflammatory disease. The purpose of this study is to evaluate the role of mean platelet volume in distinguishing adult-onset Still's disease from sepsis. METHODS: We retrospectively selected 68 patients with adult-onset Still's disease and 55 patients with sepsis between January 2015 and December 2019. Related laboratory data were collected and analyzed. RESULTS: There were no significant differences in white blood cell counts, neutrophils, lymphocytes, and C-reactive protein between adult-onset Still's disease group and sepsis group. However, patients in adult-onset Still's disease group showed higher ferritin and platelets and lower mean platelet volume and platelet distribution width than those in sepsis group (p<0.01 for both). Receiver operating characteristic curve analysis was performed to distinguish adult-onset Still's disease and sepsis. The area under the curve of mean platelet volume was 0.761 (95%CI 0.673-0.849), with a sensitivity of 79.1%, a specificity of 63.3%, and a cutoff value of 10.9 fL. In contrast, the area under the curve of combined ferritin and mean platelet volume was 0.90l (95%CI 0.837-0.965), with higher sensitivity (82.8%) and specificity (96.2%). Therefore, mean platelet volume could be used as a supplementary indicator to distinguish adult-onset Still's disease from sepsis. CONCLUSION: We suggest that mean platelet volume could be used as a supplementary biomarker for differential diagnosis of adult-onset Still's disease and sepsis in addition to ferritin.

Gold-Nanobipyramid-Based Nanotheranostics for Dual-Modality Imaging-Guided Phototherapy.

Multimodality imaging-guided therapy can improve the diagnostics and therapeutics efficiency of cancer. Herein, we developed a light-responsive nanotheranostic agent based on the indocyanine green (ICG) conjugated mesoporous silica coated gold nanobipyramid (GNB@SiO2) (denoted as GNB@SiO2-ICG) for simultaneous fluorescence (FL)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). The GNB@SiO2 with excellent photostability was used for PA imaging as well as PTT. The loaded ICG promised FL imaging and PTT. The feasibility of the cancer theranostic capability of GNB@SiO2-ICG was evaluated from cancer cells to mice. Under the guidance of FL/PA imaging, GNB@SiO2-ICG exhibited remarkably enhanced therapeutic efficacy, which could eliminate the tumor tissues completely without tumor recurrence. This well-defined nanotheranostic nanoplatform that intelligently integrates dual-modality imaging and phototherapy provides an efficient nanoplatform for cancer nanotheranostics.

Methylation analysis highlights novel prognostic criteria in human-metastasized melanoma.

Melanoma accounts for 90% of the deaths associated with cutaneous neoplasms, and the 5-year survival rate of patients with the advanced stage is about 20%. Many mechanisms are involved in melanoma progression, but dynamic epigenetic changes are likely to be critical contributors, especially for DNA methylation. However, we know little about the methylation events involved in melanoma lymph node metastasis (LNM), a deficit that is of particular concern because it has a growing incidence and mortality. To identify DNA methylated-associated changes involved in the formation of metastatic melanoma, we explored the different methylated genes (DMGs) between primary and LNM melanoma by Illumina Human Methylation 450 K BeadArray GSE44661. By integrating DNA methylation and messenger RNA expression data from The Cancer Genome Atlas database, we identified these DNA methylation biomarkers. Pathway analysis highlighted these DMGs, which were closely related to the carcinogenesis of melanoma, such as cell cycle regulation and RNA transcription process. Furthermore, according to the univariate and multivariate Cox regression analysis, we constructed a four-DMG prognostic signature model, which could precisely predict the outcome of melanoma in a more exact way. In summary, this four-DMG based risk score model successfully predicts the survival of melanoma. It is independent of other clinical characteristics and is good for prognosis prediction.

The protective effect of sinapic acid in osteoarthritis: In vitro and in vivo studies.

The anti-inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA-pretreated human chondrocytes showed lower levels of interleukin (IL)-1ß-induced IL-6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor-α (TNF-α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)-5. Furthermore, activation of nuclear factor κB (NF-κB), which was induced by IL-1ß, was also inhibited by SA through the pathway of nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.

Effect of puerarin on melanogenesis in human melanocytes and vitiligo mouse models and the underlying mechanism.

Puerarin is the major bioactive ingredient derived from the root of the Pueraria lobata (Willd.), and its antioxidative stress effects have been demonstrated in several previous studies. Moreover, Puerarin can upregulate melanin synthesis and microphthalmia-associated transcription factor (MITF) transcription by increasing cAMP level of intracellular cyclic adenosine monophosphate. Vitiligo is an acquired cutaneous disorder of pigmentation, and the pathogenesis has remained elusive. Current treatment modalities are directed towards achieving repigmentation. In this study, we found that after treating with puerarin at various concentrations of 40 µmol/L, the melanin content of human melanocytes increased significantly and the apparent level of protein and the RNA levels of MITF, tyrosinase (TYR), and tyrosinase-related protein 1 (TRP-1) were also increased. Further, puerarin was shown to inhibit phosphorylation and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) without significantly affecting p38 and c-Jun N-terminal kinase phosphorylation. These results demonstrated that puerarin stimulated melanogenesis in human melanocytes via inhibition of ERK1/2 signaling pathways, which leads to upregulation of MITF and TYR as well as TRP-1 subsequently. Additionally, mice vitiligo models with puerarin treatment showed lighter pathological changes. Therefore, we suggested that puerarin might be a potential medicine for vitiligo.

Magnetic solid-phase extraction based on graphene oxide for the determination of lignans in sesame oil.

Graphene oxide was fabricated by a simple method and applied to magnetic solid-phase extraction. In a pretreatment procedure before the sesamol, sesamin and sesamolin in sesame oil were detected by high performance liquid chromatography. Several parameters affecting the extraction efficiency were investigated, including the type and volume of desorption solvent, desorption time and the amount of sorbent. Under the optimized conditions, the detection limits of sesamol, sesamin, and sesamolin were 0.05µg/g, 0.02µg/g, and 0.02µg/g, respectively. The limits of quantification were all 0.2µg/g. The average recoveries of sesamol, sesamin, and sesamolin were 84.55%, 85.47%, 86.83%, respectively and their relative standard deviations were 1.23%, 1.33%, and 0.84%, respectively.

A Structure Identification and Toxicity Assessment of the Degradation Products of Aflatoxin B1 in Peanut Oil under UV Irradiation.

Aflatoxins, a group of extremely hazardous compounds because of their genotoxicity and carcinogenicity to human and animals, are commonly found in many tropical and subtropical regions. Ultraviolet (UV) irradiation is proven to be an effective method to reduce or detoxify aflatoxins. However, the degradation products of aflatoxins under UV irradiation and their safety or toxicity have not been clear in practical production such as edible oil industry. In this study, the degradation products of aflatoxin B1 (AFB1) in peanut oil were analyzed by Ultra Performance Liquid Chromatograph-Thermo Quadrupole Exactive Focus mass spectrometry/mass spectrometry (UPLC-TQEF-MS/MS). The high-resolution mass spectra reflected that two main products were formed after the modification of a double bond in the terminal furan ring and the fracture of the lactone ring, while the small molecules especially nitrogen-containing compound may have participated in the photochemical reaction. According to the above results, the possible photodegradation pathway of AFB1 in peanut oil is proposed. Moreover, the human embryo hepatocytes viability assay indicated that the cell toxicity of degradation products after UV irradiation was much lower than that of AFB1, which could be attributed to the breakage of toxicological sites. These findings can provide new information for metabolic pathways and the hazard assessment of AFB1 using UV detoxification.

Cadmium in Chinese Postharvest Peanuts and Dietary Exposure Assessment in Associated Population.

Cadmium (Cd) in 8698 peanut samples collected from China in 2009-2014 was studied to evaluate its contamination level, distribution, and health risk. The average Cd concentration was 0.1684 mg kg-1; the range of 2.5-97.5% was 0.0191-0.4762 mg kg-1, indicating the cadmium-contaminated peanut level was even lower. Some peanut strains for which protein contents had a significant correlation (Pearson correlation coefficient r = 0.86**) with the Cd concentration level should be of concern. Under the same soil Cd background, the difference in Cd contents in different peanut varieties is extremely significant. For example, the Cd concentration of Silihong is about 0.4522 mg kg-1, being 7 times higher than that of Zhonghua 6. According to the exposure assessment using the probabilistic simulation method, the target hazard quotients (THQs) of all groups should be below 1. The THQ range in this study was from 0.0035 to 0.0202, suggesting that there were no potential noncinogenic effects in any group.

Ion mobility spectrometry fingerprints: A rapid detection technology for adulteration of sesame oil.

A simple and rapid detection technology was proposed based on ion mobility spectrometry (IMS) fingerprints to determine potential adulteration of sesame oil. Oil samples were diluted by n-hexane and analyzed by IMS for 20s. Then, chemometric methods were employed to establish discriminant models for sesame oils and four other edible oils, pure and adulterated sesame oils, and pure and counterfeit sesame oils, respectively. Finally, Random Forests (RF) classification model could correctly classify all five types of edible oils. The detection results indicated that the discriminant models built by recursive support vector machine (R-SVM) method could identify adulterated sesame oil samples (⩾ 10%) with an accuracy value of 94.2%. Therefore, IMS was shown to be an effective method to detect the adulterated sesame oils. Meanwhile, IMS fingerprints work well to detect the counterfeit sesame oils produced by adding sesame oil essence into cheaper edible oils.

Risk Assessment on Dietary Exposure to Aflatoxin B1 in Post-Harvest Peanuts in the Yangtze River Ecological Region.

Based on the 2983 peanut samples from 122 counties in six provinces of China's Yangtze River ecological region collected between 2009-2014, along with the dietary consumption data in Chinese resident nutrition and health survey reports from 2002 and 2004, dietary aflatoxin exposure and percentiles in the corresponding statistics were calculated by non-parametric probability assessment, Monte Carlo simulation and bootstrap sampling methods. Average climatic conditions in the Yangtze River ecological region were calculated based on the data from 118 weather stations via the Thiessen polygon method. The survey results found that the aflatoxin contamination of peanuts was significantly high in 2013. The determination coefficient (R²) of multiple regression reflected by the aflatoxin B1 content with average precipitation and mean temperature in different periods showed that climatic conditions one month before harvest had the strongest impact on aflatoxin B1 contamination, and that Hunan and Jiangxi provinces were greatly influenced. The simulated mean aflatoxin B1 intake from peanuts at the mean peanut consumption level was 0.777-0.790 and 0.343-0.349 ng/(kg·d) for children aged 2-6 and standard adults respectively. Moreover, the evaluated cancer risks were 0.024 and 0.011/(100,000 persons·year) respectively, generally less than China's current liver cancer incidence of 24.6 cases/(100,000 persons·year). In general, the dietary risk caused by peanut production and harvest was low. Further studies would focus on the impacts of peanut circulation and storage on aflatoxin B1 contamination risk assessment in order to protect peanut consumers' safety and boost international trade.

Rapid on-site sensing aflatoxin B1 in food and feed via a chromatographic time-resolved fluoroimmunoassay.

Aflatoxin B1 poses grave threats to food and feed safety due to its strong carcinogenesis and toxicity, thus requiring ultrasensitive rapid on-site determination. Herein, a portable immunosensor based on chromatographic time-resolved fluoroimmunoassay was developed for sensitive and on-site determination of aflatoxin B1 in food and feed samples. Chromatographic time-resolved fluoroimmunoassay offered a magnified positive signal and low signal-to-noise ratio in time-resolved mode due to the absence of noise interference caused by excitation light sources. Compared with the immunosensing performance in previous studies, this platform demonstrated a wider dynamic range of 0.2-60 µg/kg, lower limit of detection from 0.06 to 0.12 µg/kg, and considerable recovery from 80.5% to 116.7% for different food and feed sample matrices. It was found to be little cross-reactivity with other aflatoxins (B2, G1, G2, and M1). In the case of determination of aflatoxin B1 in peanuts, corn, soy sauce, vegetable oil, and mouse feed, excellent agreement was found when compared with aflatoxin B1 determination via the conversational high-performance liquid chromatography method. The chromatographic time-resolved fluoroimmunoassay affords a powerful alternative for rapid on-site determination of aflatoxin B1 and holds a promise for food safety in consideration of practical food safety and environmental monitoring.

Development of an Enzyme-Linked Immunosorbent Assay Method Specific for the Detection of G-Group Aflatoxins.

To detect and monitor G-group aflatoxins in agricultural products, we generated class-specific monoclonal antibodies that specifically recognized aflatoxins G1 and G2. Of the final three positive and stable hybridomas obtained, clone 2G6 produced a monoclonal antibody that had equal sensitivity to aflatoxins G1 and G2, and did not cross-react with aflatoxins B1, B2, or M1. Its IC50 values for aflatoxins G1 and G2 were 17.18 ng·mL(-1) and 19.75 ng·mL(-1), respectively. Using this new monoclonal antibody, we developed a competitive indirect enzyme-linked immunosorbent assay (CI-ELISA); the method had a limit of detection of 0.06 ng·mL(-1). To validate this CI-ELISA, we spiked uncontaminated peanut samples with various amounts of aflatoxins G1 and G2 and compared recovery rates with those determined by a standard HPLC method. The recovery rates of the CI-ELISA ranging from 94% to 103% were comparable to those of the HPLC (92% to 102%). We also used both methods to determine the amounts of G-group aflatoxins in five peanut samples contaminated by aflatoxin B1-positive, and their relative standard deviations ranged from 8.4% to 17.7% (under 20%), which demonstrates a good correlation between the two methods. We further used this CI-ELISA to assess the ability of 126 fungal strains isolated from peanuts or field soils to produce G-group aflatoxins. Among these, seven stains producing different amounts of G-group aflatoxins were identified. Our results showed that the monoclonal antibody 2 G6-based CI-ELISA was suitable for the detection of G-group aflatoxins present in peanuts and also those produced by fungi.

Anti-idiotypic nanobody-phage based real-time immuno-PCR for detection of hepatocarcinogen aflatoxin in grains and feedstuffs.

Aflatoxins are a group of extremely toxic small molecules that have been involved in human hepatic and extrahepatic carcinogenesis as causative agents. Herein, we developed a real-time immuno polymerase chain reaction (IPCR) assay for the accurately quantitative detection of aflatoxins in agri-products base on a M13 phage containing aflatoxin anti-idiotypic nanobody and its encoding DNA which was used to design the specific primers. The limit of detection (LOD) of the assay is 0.02 ng/mL, which exhibits a 4-fold improvement over traditional phage ELISA. The developed method was successfully validated with the samples of corn, rice, peanut, and feedstuff, which are major aflatoxin-contaminated agri-products. And the recoveries were from 77.05 to 122.16%. For further validation, the developed assay was also compared with a reference HPLC method for the analysis of aflatoxins in corn and peanuts, and concordant results (R(2) = 0.991) were obtained. In this context, this study provides a novel opportunity to analyze aflatoxins in agri-products.