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Tobacco flavors are extensively utilized in traditional tobacco products, electronic nicotine, heated tobacco products, and snuff. To inhibit fungal growth arising from high moisture content, preservatives such as benzoic acid (BA), sorbic acid (SA), and parabens are often incorporated into tobacco flavors. Nonetheless, consuming preservatives beyond safety thresholds may pose health risks. Therefore, analytical determination of these preservatives is crucial for both quality assurance and consumer protection. For example, BA and SA can induce adverse reactions in susceptible individuals, including asthma, urticaria, metabolic acidosis, and convulsions. Parabens, because of their endocrine activity, are classified as endocrine-disrupting chemicals. Despite extensive research, the concurrent quantification of trace-level hydrophilic (BA and SA) and hydrophobic (methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben, and benzylparaben) preservatives in tobacco flavors remains challenging. Traditional liquid phase extraction coupled with high performance liquid chromatography (HPLC) often results in high false positive rates and inadequate sensitivity. In contrast, tandem mass spectrometry offers high sensitivity and specificity; however, its widespread application is limited by laborious sample preparation and significant operational costs. Therefore, it is crucial to establish a fast and sensitive sample pretreatment and analysis method for the nine preservatives in tobacco flavors. In this study, a method for the simultaneous determination of the nine preservatives (SA, BA and seven parabens) in tobacco flavor was established based on three phase-hollow fiber-liquid phase microextraction (3P-HF-LPME) technology combined with HPLC. To obtain the optimal pretreatment conditions, extraction solvent type, sample phase pH, acceptor phase pH, sample phase volume, extraction time, and mass fraction of sodium chloride, were examined. Additionally, the HPLC parameters, including UV detection wavelength and mobile phase composition, were refined. The optimal extraction conditions were as follows: dihexyl ether was used as extraction solvent, 15 mL sample solution (pH 4) was used as sample phase, sodium hydroxide aqueous solution (pH 12) was used as acceptor phase, and the extraction was carried out at 800 r/min for 30 min. Chromatographic separation was accomplished using an Agilent Poroshell 120 EC-C18 column (100 mm×3 mm, 2.7 µm) and a mobile phase comprising methanol, 0.02 mol/L ammonium acetate aqueous solution (containing 0.5% acetic acid), and acetonitrile for gradient elution. Under the optimized conditions, the nine target analytes showed good linear relationships in their respective linear ranges, the correlation coefficients (r) were ≥0.9967, limits of detection (LODs) and quantification (LOQs) were 0.02-0.07 mg/kg and 0.08-0.24 mg/kg, respectively. Under two spiked levels, the enrichment factors (EFs) and extraction recoveries (ERs) of the nine target analytes were 30.6-91.1 and 6.1%-18.2%, respectively. The recoveries of the nine target analytes ranged from 82.2% to 115.7% and the relative standard deviations (RSDs) (n=5) were less than 14.5% at low, medium and high levels. The developed method is straightforward, precise, sensitive, and well-suited for the rapid screening of preservatives in tobacco flavor samples.
Subject(s)
Liquid Phase Microextraction , Parabens , Preservatives, Pharmaceutical , Chromatography, High Pressure Liquid , Parabens/analysis , Liquid Phase Microextraction/methods , Preservatives, Pharmaceutical/analysis , Benzoic Acid/analysis , Nicotiana/chemistry , Sorbic Acid/analysis , Flavoring Agents/analysis , Tobacco Products/analysisABSTRACT
INTRODUCTION: We conducted analyses of the association between smoking and osteoporosis and osteoporotic fractures using a secondary dataset analysis of the National Health and Nutrition Examination Survey (NHANES) database and the two-sample Mendelian randomization (MR) method. METHODS: The associations between smoking and osteoporosis or osteoporotic fractures were analyzed using weighted logistic regression models for both univariate and multivariable analyses using pooled 1999-2018 NHANES data. The summary-level data of genome-wide association studies (GWAS) of smoking and osteoporosis were extracted from the IEU Open GWAS project. The inverse variance weighted method was used as the main method for the two-sample MR analysis. RESULTS: We obtained the following main findings based on the NHANES data: smoking was associated with osteoporosis according to the analyses of 30856 participants (OR=1.21; 95% CI: 1.06-1.39, p=0.004); smoking was associated with hip osteoporotic fracture according to the analyses of 30928 participants (OR=1.47; 95% CI: 1.14-1.90, p=0.004); smoking was associated with wrist osteoporotic fracture according to the analyses of 30923 participants (OR=1.33; 95% CI: 1.18-1.49, p<0.001); and smoking was associated with spine osteoporotic fracture according to the analyses of 30910 participants (OR=1.43, 95% CI: 1.18-1.73, p<0.001). In addition, we confirmed the potential causal effect of smoking on the risk of osteoporotic fracture (OR=24.5; 95% CI: 1.11-539, p=0.043) by conducting two-sample MR analyses. CONCLUSIONS: Smoking was associated with increased risks of both osteoporosis and osteoporotic fracture. Smoking showed a potential causal effect on the risk of osteoporotic fracture.
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INTRODUCTION: Traditional pesticides have poor-water solubility, high toxicity and low bioavailability. Therefore, it is of great significance for the sustainable and healthy development of the pesticide industry to develop efficient and ecofriendly new chemical pesticide products and formulations. OBJECTIVES: This study aims to synthesize a series of derivatives based on chalcone structure (HPPO), and then use the amphiphilic and self-assembly characteristics of N-succinyl-chitosan (NSCS) to prepare HPPO@NSCS nanoparticles (HPPO@NSCS NPs) in order to realize the green application of HPPO, and investigate the antifungal activity and mechanisms of HPPO@NSCS NPs. METHODS: NSCS was synthesized by structural modification using chitosan as the carrier. Based on its amphiphilic and self-assembly characteristics, HPPO-16@NSCS NPs were reasonably prepared by combining with active small molecule HPPO-16. Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy (FS) and high-performance liquid chromatography (HPLC) were used to characterize the physicochemical properties of NSCS and HPPO-16@NSCS NPs. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. The mechanism of antifungal action was discussed from the observation of pathogen morphology, fluorescence staining and enzyme activity determination. RESULTS: 28 small molecules based on chalcone structure (HPPO-1-28), NSCS and HPPO-16@NSCS were successfully synthesized. The application of HPPO-16@NSCS could impair the development, cell structure, cellular energy utilization, and metabolism pathways of the fungi. The protective effects of HPPO-16@NSCS NPs on rice leaves and leaf sheaths were 80.9 and 76.1 %, respectively, which were better than those of azoxystrobin. CONCLUSION: This study reveals that these simple chalcone derivatives can be further explored as viable antibacterial alternatives and NSCS as a novel pesticide matrix can be used for the delivery of more insoluble pesticides.
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Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. The present study aimed to probe the effect of CSRNP1 on collagen metabolism in human-derived vaginal fibroblasts. High expression of CSRNP1 was found in POP patient-derived vaginal fibroblasts in comparison to normal-derived vaginal fibroblasts. Following functional experiments revealed that CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal vaginal fibroblasts. In line with this, silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis of vaginal fibroblasts showed that differentially expressed genes affected by CSRNP1 overexpression were mainly enriched in the Wnt signaling pathway. Treatment with a Wnt pathway inhibitor DKK1 blocked CSRNP1 knockdown-caused collagen deposition. Mechanistically, CSRNP1 was identified to be a target of Snail family transcriptional repressor 2 (SNAI2). Forced expression of CSRNP1 reversed the anti-apoptotic, anti-senescent and anti-collagen loss effects of SNAI2 in normal vaginal fibroblasts exposed to H2O2 or etoposide. Our study indicates that the SNAI2/CSRNP1 axis may be a key driver in POP progression, which provides a potential therapeutic strategy for POP.
Subject(s)
Apoptosis , Cellular Senescence , Collagen , DNA Damage , Fibroblasts , Oxidative Stress , Vagina , Female , Humans , Apoptosis/genetics , Cell Proliferation , Cells, Cultured , Cellular Senescence/genetics , Collagen/metabolism , Fibroblasts/metabolism , Gene Silencing , Hydrogen Peroxide/pharmacology , Pelvic Organ Prolapse/metabolism , Pelvic Organ Prolapse/genetics , Pelvic Organ Prolapse/pathology , Snail Family Transcription Factors/metabolism , Snail Family Transcription Factors/genetics , Vagina/metabolism , Vagina/cytology , Vagina/pathologyABSTRACT
The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.
Subject(s)
Cellular Senescence , Drug Resistance, Neoplasm , Prostatic Neoplasms , Humans , Cellular Senescence/drug effects , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/metabolism , AnimalsABSTRACT
Lead-free halide perovskites as a new kind of potential candidate for photocatalytic organic synthesis have attracted much attention recently. The rational heterojunction construction is regarded as an efficient strategy to delicately regulate their catalytic performances. Herein, a semi-conductive covalent organic framework (COF) nanosheet, C4N, is employed as the functional component to construct Cs2AgBiCl6/C4N (CABC/C4N) heterojunction. It is found that the C4N nanosheets with rich surface functional groups can serve as heterogeneous nucleation sites to manipulate the growth of CABC nanocrystals and afford close contact between each other, therefore facilitate the transfer and spatial separation of photogenerated charge carriers, as verified by in situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy. Moreover, the oxygen affinity of C4N endows the heterojunctions with outstanding aerobic reactivity, thus improving the photocatalytic performance largely. The optimal CABC/C4N heterojunction delivers a thioanisole conversion efficiency of 100% after 6 h, which is 2.2 and 7.7-fold of that of CABC and C4N. This work provides a new ideal for the design and application of lead-free perovskite heterojunction photocatalysts for organic reactions.
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ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. AIM OF THE STUDY: To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. MATERIALS AND METHODS: C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type â amino-terminal peptide (Pâ NP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. RESULTS: BX improved OP in OVX mice by increasing BMD, BV/TV, serum Pâ NP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites. CONCLUSIONS: The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.
Subject(s)
Coumarins , Gastrointestinal Microbiome , Mice, Inbred C57BL , Osteoporosis , Ovariectomy , Psoralea , Animals , Psoralea/chemistry , Female , Osteoporosis/drug therapy , Coumarins/pharmacology , Coumarins/isolation & purification , Coumarins/therapeutic use , Gastrointestinal Microbiome/drug effects , Mice , Bone Density/drug effects , Metabolomics , Disease Models, Animal , Fruit , MultiomicsABSTRACT
Mitophagy is a process that selectively removes excess or damaged mitochondria and plays an important role in regulating intracellular mitochondrial mass and maintaining mitochondrial energy metabolism. TANK-binding kinase 1 (TBK1) is a multifunctional serine/threonine protein kinase, which is involved in the regulation of PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent and -independent mitophagy. Recent studies have shown that TBK1 phosphorylates the autophagy related proteins, such as optineurin (OPTN), p62/sequestosome-1, Ras-related GTP binding protein 7 (Rab7), and mediates the binding of nuclear dot protein 52 (NDP52) to UNC-51 like autophagy activating kinase 1 (ULK1) complex, as well as the binding of TAX1-binding protein 1 (TAX1BP1) to microtubule-associated protein 1 light chain 3 (LC3), thereby enhancing PINK1/Parkin-dependent mitophagy. In addition, TBK1 is a direct substrate of AMP-activated protein kinase (AMPK)/ULK1 pathway, and its activation phosphorylates dynamin-related protein 1 (Drp1) and Rab7 to promote PINK1/Parkin-independent mitophagy. This article reviews the role and mechanism of TBK1 in regulating PINK1/Parkin-dependent and -independent mitophagy.
Subject(s)
Mitophagy , Ubiquitin-Protein Ligases , AMP-Activated Protein Kinases , Autophagy , Energy MetabolismABSTRACT
BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.
Subject(s)
Chitosan , Fungicides, Industrial , Mycoses , Humans , Chitosan/chemistry , Delayed-Action Preparations/pharmacology , Fungicides, Industrial/pharmacology , Hydrophobic and Hydrophilic Interactions , Water/chemistryABSTRACT
BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.
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Malaria , Humans , Reproducibility of Results , Malaria/epidemiology , Risk Assessment , China/epidemiology , Machine LearningABSTRACT
Similar clinical features make the differential diagnosis difficult, particularly between lung cancer and pulmonary tuberculosis (TB), without pathological evidence for patients with concomitant TB infection. Our study aimed to build a nomogram to predict malignant pulmonary lesions applicable to clinical practice. We retrospectively analyzed clinical characteristics, imaging features, and laboratory indicators of TB infection patients diagnosed with lung cancer or active pulmonary TB at Xiangya Hospital of Central South University. A total of 158 cases from January 1, 2018 to May 30, 2019 were included in the training cohort. Predictive factors for lung cancer were screened by a multiple-stepwise logistic regression analysis. A nomogram model was established, and the discrimination, stability, and prediction performance of the model were analyzed. A total of 79 cases from June 1, 2019, to December 30, 2019, were used as the validation cohort to verify the predictive value of the model. Eight predictor variables, including age, pleural effusion, mediastinal lymph node, the number of positive tumor markers, the T cell spot test for TB, pulmonary lesion morphology, location, and distribution, were selected to construct the model. The corrected C-statistics and the Brier scores were 0.854 and 0.130 in the training cohort, and 0.823 and 0.163 in the validation cohort. Calibration plots showed good performance, and decision curve analysis indicated a high net benefit. In conclusion, the nomogram model provides an effective method to calculate the probability of lung cancer in TB infection patients, and it has excellent discrimination, stability, and prediction performance in detecting a malignant diagnosis of undiagnosed pulmonary lesions.
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Four trials were conducted to establish a protein and amino acid requirement model for layer chicks over 0-6 weeks by using the analytical factorization method. In trial 1, a total of 90 one-day-old Jing Tint 6 chicks with similar body weight were selected to determine the growth curve, carcass and feather protein deposition, and amino acid patterns of carcass and feather proteins. In trials 2 and 3, 24 seven-day-old and 24 thirty-five-day-old Jing Tint 6 chicks were selected to determine the protein maintenance requirements, amino acid pattern, and net protein utilization rate. In trial 4, 24 ten-day-old and 24 thirty-eight-day-old Jing Tint 6 chicks were selected to determine the standard terminal ileal digestibility of amino acids. The chicks were fed either a corn-soybean basal diet, a low nitrogen diet, or a nitrogen-free diet throughout the different trials. The Gompertz equation showed that there is a functional relationship between body weight and age, described as BWt(g) = 2669.317 × exp(-4.337 × exp(-0.019t)). Integration of the test results gave a comprehensive dynamic model equation that could accurately calculate the weekly protein and amino acid requirements of the layer chicks. By applying the model, it was found that the protein requirements for Jing Tint 6 chicks during the 6-week period were 21.15, 20.54, 18.26, 18.77, 17.79, and 16.51, respectively. The model-predicted amino acid requirements for Jing Tint 6 chicks during the 6-week period were as follows: Aspartic acid (0.992-1.284), Threonine (0.601-0.750), Serine (0.984-1.542), Glutamic acid (1.661-1.925), Glycine (0.992-1.227), Alanine (0.909-0.961), Valine (0.773-1.121), Cystine (0.843-1.347), Methionine (0.210-0.267), Isoleucine (0.590-0.715), Leucine (0.977-1.208), Tyrosine (0.362-0.504), Phenylalanine (0.584-0.786), Histidine (0.169-0.250), Lysine (0.3999-0.500), Arginine (0.824-1.147), Proline (1.114-1.684), and Tryptophan (0.063-0.098). In conclusion, this study constructed a dynamic model for the protein and amino acid requirements of Jing Tint 6 chicks during the brooding period, providing an important insight to improve precise feeding for layer chicks through this dynamic model calculation.
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BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.
Subject(s)
A Kinase Anchor Proteins , Basolateral Nuclear Complex , Depression , Lipoylation , Mice, Inbred C57BL , Animals , A Kinase Anchor Proteins/metabolism , Male , Mice , Depression/metabolism , Depression/psychology , Basolateral Nuclear Complex/metabolism , Stress, Psychological/metabolism , Behavior, AnimalABSTRACT
BACKGROUND: Qualified malaria diagnosis competency has contributed to the great achievement of malaria elimination in China. After eliminating malaria, it is still critical to the prevention of re-establishment of malaria transmission in China. This study was aimed to assess the malaria detection competency at national and provincial levels in China at the beginning of malaria post-elimination phase. METHODS: In the present study, different competency assessment activities on the laboratory malaria diagnosis were carried out for national and provincial malaria diagnostic laboratories based on the WHO scoring schedules, including malaria microscopy or nucleic acid amplification tests (NAAT), at the beginning of malaria post-elimination phase (2021-2022) in China. RESULTS: A total of 60 slides for malaria microscopy and 10 specimen for NAAT were included into the WHO External Quality Assessments of malaria parasite qualitative detection and species identification, and the scoring rate was 96.6% (microscopy: 171/177) and 85.0% (NAAT: 17/20), respectively. Moreover, 124 samples were included into the national NAAT quality assessment, and an accuracy of 87.9% (109/124) was found without significance among reference laboratories and non-reference laboratories. CONCLUSIONS: The findings suggest that there is still a need for sustained strengthening of malaria detection competency, particularly in the areas of parasite counting and detection of low-density parasitemia, to ensure prompt detection of the sources of infection and accurate identification of Plasmodium species, and contribute to case management and focus disposal, thereby effectively preventing the malaria re-establishment.
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Malaria , Plasmodium , Humans , Malaria/prevention & control , Clinical Laboratory Techniques , Laboratories , ChinaABSTRACT
The g-C3N4 (graphitic carbon nitride)/BiOI (bismuth oxyiodide) photocatalysts, boasting a unique nanomicrosphere architecture, were synthesized through a tripartite process involving heat polycondensation, hydrothermal treatment, and hybrid methods, using melamine, bismuth nitrate, and potassium iodide as starting materials. The photocatalyst was comprehensively characterized and analyzed while its efficacy in photocatalytic degradation of amaranth (AR) under various lighting conditions was investigated, and the catalytic mechanism was determined by kinetic analysis and free radical scavenging experiments. The results showed that g-C3N4 formed a strong bond with BiOI. The resulting composite catalyst retains the inherent 2D lamellar structure of g-C3N4, as well as the 3D microsphere structure of BiOI, thereby creating heterojunctions via p-n interactions. Under visible light exposure, g-C3N4/BiOI-15% demonstrated optimal catalytic performance, achieving a degradation rate of 74.64% for AR and exhibiting the highest rate constant. Radical tests confirmed that -O2- (superoxide anion) plays a crucial role as active species in the photocatalytic reaction.
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AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.
Subject(s)
Glioma , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Glioma/genetics , Glioma/therapy , Prognosis , NF-kappa B , Transforming Growth Factor beta , Tumor Microenvironment/geneticsABSTRACT
Acute pancreatitis (AP) is a common inflammatory response that occurs in the pancreas with mortality rates as high as 30 %. However, there is still no consistent and effective treatment for AP now. MicroRNA-148 was reported to be involved in AP through IL-6 signaling pathway. Therefore, we aimed to further explore the detailed mechanisms of AP, to develop more therapeutic approach for AP. Exosomes were isolated from peripheral blood mononuclear cells of 20 AP patients and 20 healthy volunteers to evaluate the abnormally expressed miRNA. Then pancreatic acinar cells (PACs) were transfected with retrovirus to overexpress miR-148a/miR-551b-5p to evaluate their function. Both miR-148a and miR-551b-5p were highly expressed in AP patients than these in healthy cases. Then overexpressing miR-551b-5p in PACs could regulate autophagy through directly binding to Baculoviral IAP Repeat Containing 6, leading to the increased secretions of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) through interleukin-1 (IL-1) signaling pathway. Moreover, overexpressing miR-148a in PACs could decrease the secretions of IL-1ß and IL-18 to modulate autophagy. The exosomal miRNA-148a and miRNA-551b-5p derived from peripheral blood mononuclear cells of AP patients may two-way mediate autophagy damage through IL-6/STAT3 signaling pathway, which participated in the AP pathogenesis. Our findings may provide new targets for the diagnosis and treatment of AP.
Subject(s)
MicroRNAs , Pancreatitis , Humans , Interleukin-18 , Acute Disease , Interleukin-6 , Leukocytes, Mononuclear , MicroRNAs/genetics , Interleukin-1beta , AutophagyABSTRACT
This study was to evaluate the efficacy of an integrated mycotoxin-mitigating agent in reducing the adverse effects of co-occurring dietary aflatoxin B1 deoxynivalenol and ochratoxin A on broiler breeder hens. 360 30-week-old Hubbard Efficiency Plus broiler breeder hens were allocated into four groups and received a basal diet (BD; Control), BD added 0.15 mg/kg aflatoxin B1+1.5 mg/kg deoxynivalenol+0.12 mg/kg ochratoxin A (Toxins), BD plus Toxins with 0.1% TOXO-XL (Toxins + XL1), and BD plus Toxins with 0.2% TOXO-XL (Toxins + XL2), respectively, for 8 weeks, and then received the same BD for another 4 weeks. Compared with control, mycotoxins decreased total egg weigh, egg laying rate, settable eggs rate, hatch of total eggs rate, egg quality, but increased feed/egg ratio and mortality rate, and impaired the liver and oviduct health during weeks 1-8 and(or) 9-12. It also increased PC and MDA concentrations, TUNEL-positive cells and IL-1ß and IL-6 expression, and decreased T-AOC, GPX and CAT activities in liver and/or oviduct. Notably, most of these negative changes were mitigated by both dosages of TOXO-XL. Generally, 0.2% TOXO-XL displayed better mitigation effects than 0.1% TOXO-XL. Conclusively, these findings revealed that TOXO-XL could mitigate the combined mycotoxins-induced toxicity on the performance, liver and oviduct health, through the regulation of redox, immunity, and apoptosis in broiler breeder hens.
Subject(s)
Mycotoxins , Humans , Animals , Female , Mycotoxins/toxicity , Mycotoxins/metabolism , Chickens/metabolism , Aflatoxin B1/toxicity , Aflatoxin B1/metabolism , Diet , Liver/metabolism , Oviducts/metabolism , Animal Feed/analysisABSTRACT
BACKGROUND: Plasmodium malariae was always neglected compared with P. falciparum and P. vivax. In the present study, we aimed to describe the epidemiology of reported cases infected with P. malariae in the past decade to raise awareness of the potential threat of this malaria parasite in China. METHODS: Individual data of malaria cases infected with P. malariae reported in China in the past decade were collected via the China Information System for Disease Control and Prevention and Parasitic Diseases Information Reporting Management System, to explore their epidemiological characteristics. Pearson Chi-square tests or Fisher's Exact Test was used in the statistical analysis. RESULTS: From 2013 to 2022, a total of 581 P. malariae cases were reported in China, and mainly concentrated in 20-59 years old group (P < 0.001), and there was no significant trend in the number of cases reported per month. Moreover, four kinds of P. malariae cases were classified, including 567 imported cases from 41 countries in 8 regions and distributed in 27 provinces (autonomous regions, municipalities) in China, six indigenous cases in a small outbreak in Hainan, seven recurrent cases in Guangdong and Shanghai, and one induced case in Shanghai, respectively. In addition, only 379 cases (65.2%) were diagnosed as malaria on the first visit (P < 0.001), and 413 cases (71.1%) were further confirmed as P. malariae cases (P = 0.002). Meanwhile, most cases sought healthcare first in the health facilities at the county and prefectural levels, but only 76.7% (161/210) and 73.7% (146/198) cases were diagnosed as malaria, and the accuracy of confirmed diagnosis as malaria cases infected with P. malariae was only 77.2% (156/202) and 69.9% (167/239) in these health facilities respectively. CONCLUSIONS: Even though malaria cases infected with P. malariae didn't account for a high proportion of reported malaria cases nationwide, the threat posed by widely distributed imported cases, a small number of indigenous cases, recurrent cases and induced case cannot be ignored in China. Therefore, it is necessary to raise awareness and improve the surveillance and response to the non-falciparum species such as P. malariae, and prevent the reestablishment of malaria transmission after elimination.