Innovative detection mechanism for deltamethrin based on a dual-emitting Fluoroprobe and its application in a smartphone-based photoelectric conversion device.

Pyrethroids are widely used insecticides worldwide, while their on-site and rapid detection still faces technological challenges. Herein, an innovative detection mechanism was designed for deltamethrin, a typical kind of type II pyrethroids, based on a dual-emitting fluoroprobe consisting of NH2-SiQDs and Eu3+. Deltamethrin can rapidly hydrolyze into 3-phenoxybenzaldehyde (3-PBD) and react specifically with fluoroprobe, causing fluorescence quenching of SiQDs while maintaining the fluorescent stability of Eu3+. Building upon the above fluorescence-responsive principle, SiQDs@Eu3+ provided satisfactorily dual-emitting signals, realizing the highly-selective and sensitive detection of deltamethrin. Correlation between the surface structure of SiQDs and their absorption spectra was in-depth unraveled by TD-DFT calculation and FT-IR analysis. As for the analytical performance, the recovery and LOD of deltamethrin in lettuce, provided by SiQDs@Eu3+, were comparable or even superior over conventional chromatographic analysis. Meanwhile, an innovative smartphone-based optical device was developed, which greatly decreased errors caused by the previously reported smartphone-based fluorescence detection.

Ratiometric fluoroprobe based on Eu-MOF@Tb3+ for detecting tetracycline hydrochloride in freshwater fish and its application in rapid visual detection.

Tetracycline hydrochloride (TCH), a prevalent antibiotic in aquaculture for treating bacterial infections, poses challenges for on-site detection. This study employed the reversed-phase microemulsion method to synthesize a uniform nano metal-organic framework (MOF) material, europium-benzene-p-dicarboxylic acid (Eu-BDC), doped with Tb3+ to form a dual-emission fluorescence probe. By leveraging the combined a-photoinduced electron-transfer (a-PET) and inner filter effect (IFE) mechanisms, high-sensitivity TCH detection in Carassius auratus and Ruditapes philippinarum was achieved. The detection range for TCH is 0.380-75 µM, with a low limit of detection (LOD) at 0.115 µM. Upon TCH binding, Eu-BDC fluorescence rapidly decreased, while Tb3+ fluorescence remained constant, establishing a ratiometric fluorescence change. Investigation into the TCH quenching mechanism on Eu-BDC was conducted using time-dependent density functional theory (TD-DFT) calculations and fluorescence quenching kinetic equations, suggesting a mixed quenching mechanism. Furthermore, a novel photoelectric conversion fluorescence detection device (FL-2) was developed and evaluated in conjunction with high-performance liquid chromatography-diode-array detection (HPLC-DAD). This is the first dedicated fluorescence device for TCH detection, showcasing superior photoelectric conversion performance and stability that reduces experimental errors associated with smartphone photography methods, presenting a promising avenue for on-site rapid TCH detection.

Circ_0001602 aggravates the progression of acute myeloid leukemia by regulating the miR-192-5p/ZBTB20 axis.

BACKGROUND: Acute myeloid leukemia (AML) is a malignant blood cancer with a poor prognosis and complex pathogenesis. Recently, the critical role of circular RNAs (circRNAs) has been demonstrated in the malignant progression of AML. This study aimed to investigate the functional role and underlying mechanism of circ_0001602 in AML development. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted for detecting the expression of circ_0001602, CCND3, microRNA-192-5p (miR-192-5p), and Zinc Finger and BTB Domain-Containing Protein 20 (ZBTB20) mRNA. RNase R assay and Actinomycin D assay were implemented to determine the characteristics of circ_0001602. Cell counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Flow cytometry was employed for assessing cell cycle distribution and apoptosis. Dual-luciferase reporter assay and RIP assay were utilized for confirming the interactions between miR-192-5p and circ_0001602 or ZBTB20. RESULTS: Circ_0001602 and ZBTB20 were upregulated and miR-192-5p level was reduced in AML tissues and cells. Depletion of circ_0001602 repressed cell proliferation and induced cell cycle arrest and apoptosis in AML cells. Functionally, circ_0001602 was identified to be the sponge of miR-192-5p, and miR-192-5p silence restored the suppressive effects of circ_0001602 knockdown on AML cell progression. Furthermore, ZBTB20 was a target of miR-192-5p, and ZBTB20 overexpression neutralized the miR-192-5p-mediated inhibiting actions on the malignant phenotypes of AML cells. Besides, circ_0001602 could sponge miR-192-5p to positively regulate ZBTB20 expression. CONCLUSION: Circ_0001602 contributed to AML cell development at least partially through modulating the miR-192-5p/ZBTB20 axis, which provided new insights for AML treatment.

[Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province].

OBJECTIVE: To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. METHODS: A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed. RESULTS: The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively. CONCLUSION: PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4.

Based on the results of epidemiological and preclinical studies, metformin can improve the prognosis of patients with malignant tumors. Studies have confirmed that metformin inhibits multiple myeloma (MM) cell proliferation and promotes apoptosis. Nevertheless, the specific mechanism remains to be elucidated. MM cells were intervened with different doses of metformin to detect cell proliferation and apoptosis. Western blotting and RT-qPCR were employed to assess the expression of METTL3, METTL14, WTAP, FTO, and ALKBH5 after metformin intervention. The microarray dataset GSE29023 was retrieved from the Gene Expression Omnibus (GEO) database and calculated using the R language (limma package) to authenticate differentially expressed genes (DEGs). The database for annotation, visualization, and integrated discovery (David) was applied for GO annotation analysis of DEGs. Subsequently, the string database and Cytoscape software were applied to construct protein-protein interaction (PPI) and DEM hub gene networks. Bioinformatics analysis and MeRIP were applied to predict and test METTL3-mediated m6A levels on mRNA of THRAP3, RBM25, and USP4 in METTL3 knocked-down cells. Then rescue experiments were performed to explore effects of METTL3 and THRAP3, RBM25, or USP4 on cell proliferation and apoptosis. The effect on MM cell xenograft tumor growth was observed by injection of metformin or/and overexpression of METTL3 in in vivo experiments. Metformin decreased cell proliferation and encouraged cell apoptosis in a dose-dependent manner. Global m6A modification was elevated in MM cells compared to normal cells, which was counteracted by metformin treatment. Furthermore, THRAP3, RBM25, and USP4 were identified as possible candidate genes for metformin treatment by GSE29023 data mining. METTL3 interference impaired m6A modification on mRNA of THRAP3, RBM25, and USP4 as well as expression levels. The mRNA stability and expression of THRAP3, RBM25, and USP4 was decreased after metformin treatment, which was reversed by METTL3 overexpression. THRAP3, RBM25 or USP4 knockdown reversed the assistance of METTL3 overexpression on the malignant behavior of MM cells. Finally, upregulation of METTL3 was shown to exert facilitative effects on xenograft tumor growth by blocking metformin injection. The present study demonstrates that metformin can repress the expression of THRAP3, RBM25, and USP4 by inhibiting METTL3-mediated m6A modification, which in turn hamper cell proliferation and promotes cell apoptosis.Abbreviations: multiple myeloma (MM), Gene Expression Omnibus (GEO), differentially expressed genes (DEGs), database for annotation, visualization and integrated discovery (David), protein-protein interaction (PPI), epithelial­mesenchymal transition (EMT), methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), wilms tumor 1-associated protein (WTAP), methyltransferase like 16 (METTL16), acute myeloid leukemia (AML), non-small lung cancer (NSCLC), glioma stem cells (GSCs), normal bone marrow-derived plasma cells (nPCs), false discovery rate (FDR), biological process (BP), optical density (OD), horseradish peroxidase (HRP), M6A RNA immunoprecipitation assay (MeRIP).

Lenvatinib for effectively treating antiangiogenic drug-resistant nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) clinical trials show that antiangiogenic drugs (AADs) fail to achieve the expected efficacy, and combining AAD with chemoradiotherapy does not show superiority over chemoradiotherapy alone. Accumulating evidence suggests the intrinsic AAD resistance in NPC patients with poorly understood molecular mechanisms. Here, we describe NPC-specific FGF-2 expression-triggered, VEGF-independent angiogenesis as a mechanism of AAD resistance. Angiogenic factors screening between AAD-sensitive cancer type and AAD-resistant NPC showed high FGF-2 expression in NPC in both xenograft models and clinical samples. Mechanistically, the FGF-2-FGFR1-MYC axis drove endothelial cell survival and proliferation as an alternative to VEGF-VEGFR2-MYC signaling. Genetic knockdown of FGF-2 in NPC tumor cells reduced tumor angiogenesis, enhanced AAD sensitivity, and reduced pulmonary metastasis. Moreover, lenvatinib, an FDA recently approved multi-kinase inhibitor targeting both VEGFR2 and FGFR1, effectively inhibits the tumor vasculature, and exhibited robust anti-tumor effects in NPC-bearing nude mice and humanized mice compared with an agent equivalent to bevacizumab. These findings provide mechanistic insights on FGF-2 signaling in the modulation of VEGF pathway activation in the NPC microenvironment and propose an effective NPC-targeted therapy by using a clinically available drug.

A Synergistic Association Between Inflammation, Malnutrition, and Mortality in Patients With Diabetics.

Background: Although inflammation is a known predictor for poor prognosis in patients with diabetics, few data report the synergistic association between inflammation, malnutrition, and mortality in patients with diabetics. We aim to explore whether malnutrition modifies the predictor of inflammation on prognosis. Methods: Nutritional status and inflammation were measured in 6,682 patients with diabetics undergoing coronary angiography or percutaneous coronary intervention between January 2007 to December 2018 from Cardiorenal Improvement Registry. Malnutrition was defined as Controlling Nutritional Status (CONUT) score, which was more than 1. High-sensitivity C-reactive protein (hs-CRP) exceeding the median was assessed as a high-risk inflammation. Cox regression models were used to estimate hazard ratios (HR) for mortality across combined hs-CRP and CONUT score categories. Results: During a median follow-up of 5.0 years (interquartile range: 3.0-7.6 years), 759 (11.36%) patients died. The mortality of the four groups (normal nutrition and low hs-CRP level; normal nutrition and high hs-CRP level; malnutrition and low hs-CRP level; and malnutrition and high hs-CRP level) were 7.29, 7.12, 10.71, and 17.31%, respectively. Compared with normal nutrition and low hs-CRP level, an isolated condition of either malnutrition or high hs-CRP level was not associated with any significant risk for all-cause mortality. However, concomitant presence of both high hs-CRP level and malnutrition condition was associated with a significantly increased risk of all-cause mortality (HR: 1.51; 95% CI: 1.20-1.89; p < 0.001). The p-value for interaction between nutritional status and hs-CRP level on all-cause mortality was 0.03. Conclusion: The interplay of inflammation and malnutrition in patients with diabetics significantly amplifies the deleterious effects of each as distinct disease entities. A prospective randomized clinical trial is needed in the future to verify the results.

Impact of the Malnutrition on Mortality in Patients With Osteoporosis: A Cohort Study From NHANES 2005-2010.

Background: Osteoporosis is the most common metabolic bone disease. Recent studies have shown that malnutrition can promote the development of osteoporosis. However, the incidence of malnutrition in patients with osteoporosis and the relationship between malnutrition and all-cause mortality has not been adequately studied. Therefore, our study investigated the relationship between malnutrition and all-cause mortality in patients with osteoporosis. Methods: We analyzed data on 7,700 adults ≥20 years of age during National Health and Nutrition Examination Survey (NHANES) 2005-2010. Each patient was assigned to one of three groups: normal nutritional status, mild malnutrition, and moderate to severe malnutrition. Survival curves and univariate and multivariable cox regressions based on the NHANES recommended weights were used to assess the association between malnutrition status and mortality. Moreover, cox proportional hazards regression analyses were performed on the matched pairs. Results: Overall, 7,700 eligible individuals with osteoporosis were included in the final analysis, and the mean age was 52.0 ± 0.4 years. From the Kaplan-Meier curves for long-term all-cause mortality of malnutrition, worsening malnutrition status was associated with higher incidence of all-cause mortality. In the fully adjusted models, the adjusted hazard ratio (aHR) was 1.54 [95% confidence interval (CI), 1.02-2.31, p = 0.039] at mild malnutrition status and 2.70 (95%CI, 1.95-3.74, p < 0.001) at moderate to severe malnutrition status. The cox model after matching indicated that malnutrition was still a high mortality risk than no malnutrition (aHR = 2.23, 95% CI, 1.66-3.01, p < 0.001). Conclusions: Poor malnutrition status, common in osteoporotic patients, is strongly associated with a risk for all-cause mortality comparable to that seen with normal nutritional status. These findings highlight the importance of risk stratification for nutritional status in osteoporotic patients and the implementation of strategies that is now available to help prevent malnutrition in these patients.

Predictors and Mortality for Worsening Left Ventricular Ejection Fraction in Patients With HFpEF.

Background: Definitions of declined left ventricular ejection fraction (LVEF) vary across studies and research results concerning the association of mortality with declined LVEF are inconsistent. Thus, this study aimed to assess the impact of early worsening LVEF on mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and to establish independent predictors of early worsening LVEF. Methods and Results: A total of 1,418 consecutive patients with HFpEF with LVEF remeasurement from the Cardiorenal Improvement registry were included in this study. Worsening LVEF was defined as an absolute decline ≥ 5% from baseline LVEF within 3 to 12 months after discharge. The Cox and logistic regression analyses were performed to assess prognostic effects and predictors for worsening LVEF, respectively. Among 1,418 patients with HFpEF, 457 (32.2%) patients exhibited worsening LVEF. During a median follow-up of 3.2 years (interquartile range: 2.3-4.0 years), 92 (6.5%) patients died. Patients with HFpEF with worsening LVEF had higher mortality relative to those with nonworsening LVEF [9.2 vs. 5.2%; adjusted hazard ratio (aHR): 2.18, 95% CI: 1.35-3.52]. In the multivariate binary logistic regression analysis, baseline left ventricular end-diastolic dimension (LVEDD), LVEF, high-density lipoprotein cholesterol (HDL-C), atrial fibrillation (AF), and diabetes mellitus (DM) emerged as predictive factors of worsening LVEF. Conclusion: This study demonstrated that about one out of three patients with HFpEF experiences worsening LVEF during follow-up, which is associated with 2.2-fold increased mortality. Increased LVEDD and LVEF, low HDL-C levels, AF, and DM were predictors of worsening LVEF. Further studies are needed to prospectively assess the efficacy of early active management on prognosis in patients with HF with worsening LVEF. Registration: ClinicalTrials.gov, identifier NCT04407936.

CRISPR/Cas9 (D10A) nickase-mediated Hb CS gene editing and genetically modified fibroblast identification.

This study investigated whether CRISPR/Cas9 (D10A) nickase-mediated gene editing can correct the aberrant Hb Constant Spring mutation (Hb CS or HBA2: c.427 T > C) in fibroblasts. Vectors for repairing the α-globin-encoding gene, HBA2:c.427 T > C mutation, includingthe CRISPR/Cas9(D10A)-sg plasmid and donor with homology arms, were constructed and used to perform gene editing in patient-derived fibroblasts. We subsequently analyzed the genetic correction, the gene editing efficiency and off-target effect. Sequencing analysis and the BamHI assay showed that HB CS mutant cells were repaired with Hb CS point mutations, the editing efficiency was 4.18%~9.34% and no off-target effects were detected. The results indicate that the HB CS mutant gene is effectively repaired by the CRISPR/Cas9 (D10A)system, which may enable truly personalized therapy for precise repair of α-thalassemia.

miRNA-425-5p enhances diffuse large B cell lymphoma growth by targeting PTEN.

BACKGROUND: At present, cancer is one of the greatest threats to mankind, and is associated with the highest rates of morbidity and comorbidity. Recently, the advancements in molecular biology have led to an in-depth understanding of the underlying pathophysiology, which may further impact the lead time in the context of early discovery and effective therapy of cancer. Therefore, the present study proposes a better understanding of the role of micro(miR)-425-5p in diffuse large B-cell lymphoma (DLBC). METHODS: qRT-PCR was carried out to detect the relevant proteins, miRNA and mRNA RNA gene expression in DLBC cells. The effect of miR-425-5p on DLBC growth was examined by CCK-8 and colony formation assays. The binding relationship between genes was verified by dual-luciferase reporter gene assay. RESULTS: We demonstrated how the over-expression of miR-425-5p can lead to increased progression of DLBC by increasing the cellular proliferation rate and colony-forming ability. Additionally, we also found that the expression of miR-425-5p could be significantly inhibited on the basis of phosphatase and tensin homolog (PTEN) signaling pathways. CONCLUSIONS: The present study concludes that miR-425-5p is responsible for the oncogenic progression and relapse of DLBC tumorigenesis via PTEN/PI3K signaling, which can thus be effectively used to achieve better therapeutic outcomes.

T follicular helper cell-mediated IL-21 production suppresses FOXP3 expression of T follicular regulatory-like cells in diffuse large B cell lymphoma patients.

Based on CD25 expression, T follicular helper cells (Tfh) could be divided into T follicular regulatory (Tfr)-like subset (CD25+CD4+CXCR5+) and CD25- Tfh subset (CD25-CD4+CXCR5+). Patients with diffuse large B cell lymphoma (DLBCL) display high level of Tfr-like cells in blood and tumor. This Tfr-like subset could suppress CD8 T cell response while promote tumor cell proliferation. In this study, we investigated the transcription factors and regulatory elements associated with Tfr-like cells in DLBCL patients. Both circulating and tumor-infiltrating Tfr-like cells presented slightly higher Blimp-1 expression and significantly higher Foxp3 expression than the CD25- Tfh subset. As the IL-2 receptor, CD25 could be moderately upregulated in stimulated CD25- Tfh cells. However, stimulated CD25- Tfh cells could not upregulate Foxp3, indicating that the distinction between Foxp3-low CD25-CXCR5+CD4+ T cells and Foxp3-high CD25+CXCR5+CD4+ T cells was not due to differences in stimulation status. Regarding cytokine production, while both Tfr-like and CD25- Tfh cells upregulated IL-21 and IL-10 during stimulation, the CD25- Tfh cells presented significantly higher IL-21 and lower IL-10 expression than the Tfr-like cells, and the TGF-ß expression was only increased in Tfr-like cells. Interestingly, IL-21 secreted from CD25- Tfh cells negatively regulated the expression of Foxp3 and IL-10 of autologous Tfr-like cells. Together, these results demonstrated that the Tfr-like and CD25- Tfh subsets of circulating Tfh cells presented different functions and should be investigated separately.

Anti-Neutrophil Cytoplasmic Antibody-Negative Central Nervous System Granulomatosis With Polyangiitis and Its Clinical Characteristics.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis occasionally affecting central nervous system (CNS), and GPA patients with initial CNS symptoms are even rarer, whose diagnosis is further confused by an absence of positive antineutrophil cytoplasmic antibody. The authors described the characteristics of antineutrophil cytoplasmic antibody -negative GPA with CNS onset in a patient and discussed on its management, which may contribute to future diagnosis and treatment of patients with similar conditions.