A high-accuracy lightweight network model for X-ray image diagnosis: A case study of COVID detection.

The Coronavirus Disease 2019(COVID-19) has caused widespread and significant harm globally. In order to address the urgent demand for a rapid and reliable diagnostic approach to mitigate transmission, the application of deep learning stands as a viable solution. The impracticality of many existing models is attributed to excessively large parameters, significantly limiting their utility. Additionally, the classification accuracy of the model with few parameters falls short of desirable levels. Motivated by this observation, the present study employs the lightweight network MobileNetV3 as the underlying architecture. This paper incorporates the dense block to capture intricate spatial information in images, as well as the transition layer designed to reduce the size and channel number of the feature map. Furthermore, this paper employs label smoothing loss to address the inter-class similarity effects and uses class weighting to tackle the problem of data imbalance. Additionally, this study applies the pruning technique to eliminate unnecessary structures and further reduce the number of parameters. As a result, this improved model achieves an impressive 98.71% accuracy on an openly accessible database, while utilizing only 5.94 million parameters. Compared to the previous method, this maximum improvement reaches 5.41%. Moreover, this research successfully reduces the parameter count by up to 24 times, showcasing the efficacy of our approach. This demonstrates the significant benefits in regions with limited availability of medical resources.

Causal effects of genetically determined blood metabolites on multiple myeloma: a Mendelian randomization study.

Previous studies have shown that metabolites play an important role in phenotypic regulation. However, the causal relationship between metabolites and multiple myeloma has not been adequately investigated. Here, we attempt to explore the causal effects of genetically determined blood metabolites on multiple myeloma. The large-scale public blood metabolites and multiple myeloma datasets from independently published genome-wide association studies (GWAS) were used to explore the causal relationship between each genetically determined blood metabolite and multiple myeloma through inverse variance weighted (IVW), weighted median, MR-Egger and mode-based estimation methods. Sensitivity tests were performed to evaluate the stability and reliability of the results by MR-Egger regression and leave-one-out methods. Metabolic pathway analysis was further explored using filtered data. Statistical analyses were all performed in R. Among 452 metabolites, ten known metabolites and three unknown metabolites had significant causal relationship with multiple myeloma (P < 0.05). Four known metabolites, 3-methyl-2-oxovalenate, oxidized bilirubin, isovalerylcarnitine and glutamine carnitine, reached statistical significance in IVW models. Metabolic pathways analysis identified four significant pathways. The occurrence of multiple myeloma may have a causal relationship with these four metabolites, and there are four metabolic pathways that are also related to the occurrence of multiple myeloma. This can provide new ideas for exploring early screening and treatment of multiple myeloma.

Lymphatic clearance is the main drainage route of lamotrigine-loaded micelles following delivery to the brain.

OBJECTIVES: This study aimed to investigate the clearance pathways of lamotrigine (LTG)-loaded micelles by intranasal administration and intracerebral injection in the brain and whether nanoparticles can induce the inflammation promoted by interleukin-6 (IL-6), accelerating the phagocytosis of drug particles in the brain and drainage through lymphatics. METHODS: The drug concentrations in the deep cervical lymph node, superficial cervical lymph node, brain tissues and jugular vein, the pharmacokinetic parameters, and the concentrations of IL-6 in deep cervical lymph node and brain tissues were investigated following UPLC/MS, DAS3.0, ELISA statistically analysed. KEY FINDINGS: The AUC0- t of deep cervical lymph node after intranasal and intracerebral injection was 1.93, 2.77, 1.34 times and 3.06, 16.4, 3.34 times higher compared with the superficial cervical lymph node, jugular vein and brain tissue, respectively. After intranasal administration of lamotrigine-loaded micelles for 30 min, the IL-6 concentrations in deep cervical lymph node and brain tissue were significantly increased (P < 0.05). CONCLUSIONS: These results suggested that lamotrigine micelles were primarily cleared from the brain by lymphatics rather than blood clearance. Also, the nanoparticle induced the increase in IL-6 level after entering the brain suggested that nanoparticles might induce the inflammation promoted by IL-6 in the brain, accelerating the clearance of drug particles in the brain and drainage through lymphatics.

Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation by inhibiting Th17-associated pro-inflammatory gene expression.

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity. We investigated the therapeutic effects of green tea extract (GTE) and its major component, epigallocatechin-3-gallate (EGCG), on a murine model of experimental autoimmune uveoretinitis (EAU). Oral administration of GTE, EGCG, dexamethasone, or water, which started 5 days before the induction, was fed every two days to each group. On day 21 post induction, the eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT), fundus fluorescein angiography (FFA) and electroretinography (ERG) prior to sacrificing the animals for histological assessments and gene expression studies. Retinal-choroidal thicknesses (RCT) and major retinal vessel diameter were measured on OCT sections and FFA images, respectively. Comparing to water-treated EAU animals, GTE attenuated uveitis clinical manifestations, RCT increase (1.100 ± 0.013 times vs 1.005 ± 0.012 times, P < 0.001), retinal vessel dilation (308.9 ± 6.189 units vs 240.8 units, P < 0.001), ERG amplitudes attenuation, histopathological ocular damages, and splenomegaly in EAU mice. The therapeutic effects of GTE were dose dependent and were comparable to dexamethasone. EGCG, a major active constituent of GTE, partially alleviated uveitic phenotypes including recovering visual function. Th-17 associated pro-inflammatory gene [interleukin 1 beta (IL-1ß), IL-6, IL-17A, and tumor necrosis factor alpha (TNF-α)] expressions were down regulated by GTE and EGCG treatments, which showed no detectable morphological defects in liver and kidney in non-induced and EAU mice. Our findings suggest that GTE consumption can serve as a potent therapeutic agent as well as a food supplement for developing alternative treatments against autoimmune uveitis.

GSK-3ß inhibits autophagy and enhances radiosensitivity in non-small cell lung cancer.

BACKGROUND: Radiotherapy is one of the most common and effective treatment methods for cancer, and improving the radiosensitivity of tumor tissues during the treatment process is vital. We report the mechanisms of glycogen synthase kinase 3 (GSK-3) ß-regulated autophagy and the effects of autophagy on radiosensitivity in non-small cell lung cancer (NSCLC). METHOD: Immunohistochemical staining was performed to determine GSK-3ß tissue expression in 89 NSCLC patients with follow-up data and the expression status of GSK-3ß and autophagy in NSCLC tissues after X-ray radiotherapy. Western blots were used to quantitate changes in autophagy-related protein expression after A549 cells were treated with GSK-3ß inhibitors and after H460 cells were transfected with GSK-3ß mutants with different activities and X-ray irradiated. Clonogenic assays were used to measure the effect of autophagy on cellular proliferation. RESULTS: GSK-3ß expression positively correlated with NSCLC differentiation (P < 0.05), and GSK-3ß negativity was associated with a better prognosis in 89 NSCLC patients. After X-ray irradiation, the expression levels of GSK-3ß and p62 were decreased in NSCLC tissues, and the expression levels of the autophagy-related protein LC3 were increased. A549 and H460 cells were selected as representative GSK-3ß-high and GSK-3ß-low expression cell lines. After transfecting H460 cells with different GSK-3ß mutants [wild type GSK-3ß (GSK-3ß-WT), constitutively active GSK-3ß (GSK-3ß-S9A), and catalytically inactive GSK-3ß (GSK-3ß-K85R)] and subjecting these cells to X-ray irradiation, AMPK and LC3 expression levels decreased, and p62 expression levels increased. These effects were particularly significant for the GSK-3ß-S9A mutant. In A549 cells, after GSK-3ß inhibition and X-ray irradiation, AMPK and LC3 protein expression levels increased. Moreover, when autophagy was inhibited, cell proliferation decreased. CONCLUSION: Our studies revealed that GSK-3ß expression is associated with NSCLC differentiation, and patients with GSK-3ß-negative tumors had a better prognosis. X-ray irradiation inhibited GSK-3ß expression and promoted autophagy. Therefore, GSK-3ß inhibits autophagy and enhances the radiosensitivity of NSCLC cells.

Preparation of bio-based magnetic adsorbent and application for efficient removal of Cd(II) from water.

A novel magnetic bio-adsorbent (MCIA) was developed, characterized and tested for its Cd(II) removal from aqueous solution. MCIA could be easily separated from the solution after equilibrium adsorption due to its super-paramagnetic property. The functional and magnetic bio-material was an attractive adsorbent for the removal of Cd(II) from aqueous solution owing to the abundant adsorption sites, amino-group and oxygen-containing groups on the surface of Cyclosorus interruptus. The experimental results indicated that the MCIA exhibited excellent adsorption ability and the adsorption process was spontaneous and endothermic. The adsorption isotherm was consistent with the Langmuir model. The adsorption kinetic fitted the pseudo-second-order model very well. The maximum adsorption capacity of Cd(II) onto MCIA was 40.8, 49.4, 54.6 and 56.6 mg/g at 293, 303, 313 and 323 K, respectively. And the MCIA exhibited an excellent reusability and impressive regeneration. Therefore, MCIA could serve as a sustainable, efficient and low-cost magnetic adsorbent for Cd(II) removal from aqueous solution.

LncRNA-NEF antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/ß-catenin signaling.

Emerging evidence indicates that the long noncoding RNAs extensively participate in cancer progression. Nevertheless, the molecular pathogenesis of how these lncRNAs regulate tumorigenesis has not been fully elucidated especially in hepatocellular carcinoma (HCC). Here, we sought to define the role of a novel lncRNA named lncRNA-NEF in modulating epithelial to mesenchymal transition (EMT) in HCC. It was found that the lncRNA-NEF was transcriptionally activated by EMT suppressor FOXA2 and frequently downregulated in HCC cell lines as well as clinical specimens. Although enhanced expression of lncRNA-NEF did not affect tumor cell growth, ectopic expression of lncRNA-NEF significantly suppressed EMT program and cell migration. Animal studies validated that lncRNA-NEF alleviated in vivo tumor metastasis and protected mice from tumor-induced mortality. Interestingly, we verified that lncRNA-NEF acted as a novel activator of its neighbor gene FOXA2, which formed a positive feedback loop. Subsequent studies revealed that lncRNA-NEF physically interacted with ß-catenin to increase the binding of GSK3ß with ß-catenin and therefore promoted the inhibitory phosphorylation of ß-catenin, leading to the suppression on Wnt/ß-catenin signaling and activation of FOXA2 expression. Hence, our findings illustrated a novel feedback loop including FOXA2 and its neighboring gene lncRNA-NEF, which might provide mechanistic insights into the metastatic progress of HCC.

mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus.

PURPOSE: This study aimed to develop a novel methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG) distribution in the hippocampus. METHODS: LTG-loaded mPEG-PLA/TPGS mixed micelles and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics, particle size, surface morphology, and release behavior in vitro were researched. Then, a microdialysis sampling technique coupled with two validated chromatographic systems was developed for the continuous measurement of the protein-unbound form of LTG in the rat plasma and hippocampus after administering two kinds of micelles and LTG solution intranasally. RESULTS: The drug loading and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with optimal formulation were 36.44%±0.14%, 39.28%±0.26%, 122.9, and 183.5 nm, respectively, with a core-shell structure. The cumulative release rate in vivo of LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained release while that of LTG-loaded micelles was 80.61% at 6 hours. The Tmax and area under concentration-time curve from zero to time of last quantifiable concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min⋅µg)/L in the hippocampus, respectively. CONCLUSION: The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy.

Removal of mercury ions from aqueous solution by thiourea-functionalized magnetic biosorbent: Preparation and mechanism study.

A novel magnetic bio-material (MCIT) was synthesized via coupling reaction and functional modification after load of Fe3O4 nano-particle on the puckered surface of cyclosorus interruptus (CI). The synthesized material was characterized by fourier transform infrared (FTIR), field emission scanning electron microscope (FE-SEM), X-ray photoelectron spectroscopy (XPS) and X-ray powder diffractometer (XRD). The influence factors like pH, temperatures, contact time, initial concentration and cycle times on the adsorption of Hg (II) in aqueous solution were studied. Adsorption isotherm, kinetics, selectivity and mechanism were investigated. The results indicated that the isotherm model well agreed with monolayer adsorption model. The adsorption process could be divided into three steps, which included a fast step controlled by chemical adsorption, a slow step limited by intraparticle diffusion and an equilibrium stage. The maximum adsorption capacity of Hg (II) was 385.3mg/g at 318K. MCIT possessed high reusability (retained 93% after five successive cycles) and sharply magnetic nature (9.5emu/g), which endowed it easy and efficient separation from aqueous solution.

Quantitative Characterization of Autoimmune Uveoretinitis in an Experimental Mouse Model.

Purpose: To accurately evaluate the autoimmune inflammation, we aim to develop three quantitative measurements to monitor the inflammatory changes in the retina: retinal-choroidal thickness, major retinal vessel diameter, and electroretinography amplitudes. Methods: During a 21-day experimental period, eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography, fundus fluorescein angiography, and electroretinography in living mice, which were then subsequently killed for histologic assessments. Results: On day 21 postimmunization, inflammation was observed both in vivo and in vitro. Fold change of retinal-choroidal thickness and major retinal vessel diameter in experimental autoimmune uveoretinitis mice were significantly greater than controls (P < 0.001). Both scotopic and photopic electroretinography amplitudes were significantly attenuated when compared with control mice (P < 0.01). Our results showed that these three quantifiable indicators provided an objective and accurate evaluation of autoimmune inflammation, which are in good correlations with the reported clinical and histopathologic scoring systems (P < 0.05). Conclusions: These three indicators will be useful to detect the small but significant differences in the severity of experimental autoimmune uveoretinitis for future longitudinally therapeutic studies.

Methodological assessment of the reduction of the content of impurities in nimodipine emulsion via the use of 21 amino acid protection.

PURPOSE: The present study examined the factors affecting the content of impurities of nimodipine (NMP) emulsion and the associated methods of compound protection. METHODS: Destructive testing of NMP emulsion and its active pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used to study the content of impurities in two phases. The impurity of NMP was measured under different potential of hydrogen (pH) conditions, antioxidants and pH-adjusting agents. RESULTS: Following destruction, the degradation of NMP notably occurred in the basic environment. The consumption of the pH-adjusting agent NaOH was proportional to the production of impurities since the inorganic base and/or acid promoted the degradation of NMP. The organic antioxidants, notably amino acids with an appropriate length of intermediate chain and electron-donating side group, exhibited improved antioxidant effects compared with inorganic antioxidants. The minimal amount of impurities was produced following addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of the pH to a range of 7.5-8.0 in the presence of acetic acid solution. CONCLUSION: NMP was more prone to degradation in an oxidative environment, in an aqueous phase and/or in the presence of inorganic pH-adjusting agents and antioxidants. The appropriate antioxidant and pH-adjusting agent should be selected according to the chemical structure, while destructive testing of the drug is considered to play the optimal protective effect.

Organically directed iron sulfate chains: structural diversity based on hydrogen bonding interactions.

Six organically directed 1-D iron sulfates hydrated and hydrolyzed to different extents have been prepared hydrothermally. [C2H10N2]1.5[Fe(SO4)(3)].2H2O (I), [C2H10N2][Fe(SO4)2(OH)].H2O (II), [C6H18N2]0.5[Fe(SO4)2(H2O)2] (III), and [C6H18N2]0.5[Fe2(SO4)(H2O)4(OH)].H2O (V) possess the linear topological structures observed in ferrinatrite, sideronatrite, kröhnkite, and copiapite minerals, respectively. [C4H12N2][Fe2(SO4)3(OH)2(H2O)2].H2O (IV) shows a novel linear structure that can be regarded as a hybrid of the tancoite and butlerite types. [C6N4H22]0.5[Fe(SO4)2(OH)].2H2O (VI) adopts a cis configuration, compared with II, to give a rare inorganic helical iron sulfate chain which is a new member of the organically directed transitional metal sulfates. The results reveal that the starting molar proportion of the reactants and the type of amines are critical for the structural motif. There is an obvious relationship between the constitution of chains and the type of amino groups, involving the amount of N-H...O hydrogen bonds.