Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis.

BACKGROUND: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid. METHODS: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions. RESULTS: Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 µg per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 µg per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 µg per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater. CONCLUSIONS: This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).

High temperature and humidity in the environment disrupt bile acid metabolism, the gut microbiome, and GLP-1 secretion in mice.

High temperature and humidity in the environment are known to be associated with discomfort and disease, yet the underlying mechanisms remain unclear. We observed a decrease in plasma glucagon-like peptide-1 levels in response to high-temperature and humidity conditions. Through 16S rRNA gene sequencing, alterations in the gut microbiota composition were identified following exposure to high temperature and humidity conditions. Notably, changes in the gut microbiota have been implicated in bile acid synthesis. Further analysis revealed a decrease in lithocholic acid levels in high-temperature and humidity conditions. Subsequent in vitro experiments demonstrated that lithocholic acid increases glucagon-like peptide-1 secretion in NCI-H716 cells. Proteomic analysis indicated upregulation of farnesoid X receptor expression in the ileum. In vitro experiments revealed that the combination of lithocholic acid with farnesoid X receptor inhibitors resulted in a significant increase in GLP-1 levels compared to lithocholic acid alone. In this study, we elucidate the mechanism by which reduced lithocholic acid suppresses glucagon-like peptide 1 via farnesoid X receptor activation under high-temperature and humidity condition.

Protective effect of Helianthus annuus seed byproduct extract on ultraviolet radiation-induced injury in skin cells.

Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1ß, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK-ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.

Protein N-glycosylation aberrations and glycoproteomic network alterations in osteoarthritis and osteoarthritis with type 2 diabetes.

Whether the relationship between type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) can be solely attributed to the shared risk factors, such as obesity, remains controversial. Several studies have revealed the critical role of abnormal glycosylation in the pathogenesis of OA and T2DM. Therefore, we speculate that T2DM may contribute to the pathogenesis of OA through the intrinsic mechanisms of N-glycosylation aberrations. Using N-glycoproteomics, we compared the changes in N-glycosylated protein abundance in cartilage samples from patients with OA without and with T2DM (DM-OA), and from patients with traumatic joint injury (NC) as controls. We identified 847 N-glycosylation sites corresponding to 729 peptides fragments from 374 proteins. The number of N-glycosylated proteins in the DM-OA group tended to decrease compared with that in the OA and NC groups. We identified 22 upregulated and 1 down-regulated N-glycosylated peptides in the OA group compared to the NC group, while only fibronectin 1 (FN1) at position N1007, cartilage intermediate layer protein 1 (CILP) at N346, and collagen type VI alpha 1 chain (COL6A1) at N804, were also identified in the DM-OA group. Compared to the OA group, the downregulation of secreted protein acidic and rich in cysteine (SPARC) at N116, collagen type VI alpha 1 chain (COL6A2) at N785, and asporin (ASPN) at N282, and the upregulation of complement component C8 alpha chain (C8α) at N437, were the most remarkable alterations in the DM-OA group. The differentially expressed N-glycosylated proteins between the OA and DM-OA groups were mainly located extracellularly and enriched in the KEGG pathways involving PI3K/Akt signaling, focal adhesion, and ECM-receptor interaction. Their predicted protein-protein interactions were also depicted. We were thus able to show the general characteristics of N-glycosylation aberrations in OA and DM-OA. Moreover, the upregulated glycosylated complement C8α in the DM-OA group might augment membrane attack complex activity, thereby exacerbating cartilage destruction. Although further confirmation is required, our hypothesis proposes a possible explanation for the deduction that T2DM is an independent risk factor for OA.

Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy.

BACKGROUND: Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line clinical treatment for GC therapy, but chemotherapy resistance remains a severe clinical challenge. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but the function of ZnO-NP in GC development is still unclear. AIM: To explore the effect of ZnO-NP on chemotherapy resistance during GC progression. METHODS: ZnO-NP was synthesized, and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, transwell assays, wound healing assays, flow cytometry, and Western blot analysis in GC cells and DDP-resistant GC cells, and by tumorigenicity analyses in nude mice. RESULTS: Our data revealed that ZnO-NP was able to inhibit proliferation, migration, and invasion and induce apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the half maximal inhibitory concentration (IC50) of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in DDP-resistant GC cells, as demonstrated by elevated light chain 3-like protein 2 (LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo. CONCLUSION: We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC. ZnO-NP may serve as a potential therapeutic candidate for GC treatment. The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.

High temperature anionic Fe(III) spin crossover behavior in a mixed-valence Fe(II)/Fe(III) complex.

Two ion-pair Fe(iii) complexes (PPh4)[FeIII(HATD)2]·2H2O (1, H3ATD = azotetrazolyl-2,7-dihydroxynaphthalene) and [FeII(phen)3][FeIII(HATD)2]2·3DMA·3.5H2O (2, phen = 1,10-phenanthroline, DMA = N,N-dimethylformamide) were synthesized by employing the tridentate ligand H3ATD. Crystal structure analyses reveal that complexes 1 and 2 consist of FeIII ions in an octahedral environment where a FeIII ion is coordinated by two HATD2- ligands forming the [FeIII(HATD)2]- core. The shortest cationanion distance between the phosphorus ion of the (PPh4)+ cation and the ferric ion of the [FeIII(HATD)2]- anion is 13.190 Å in complex 1, whereas that between the ferrous ion of the [FeII(Phen)3]2+ cation and the ferric ion of the [FeIII(HATD)2]- anion is 7.821 Å in complex 2. C-HC and C-HO hydrogen interactions between the [FeII(phen)3]2+ cation and the [FeIII(HATD)2]- anion are observed in 2. Face-to-face π-π stacking interactions between naphthalene rings with the separated interplanar center to center distances of 3.421-3.680 Å were observed, which result in a one-dimensional supramolecular chain in complexes 1 and 2. Magnetic measurements show that complex 1 is in the low-spin (LS) state below 500 K, whereas 2 undergoes a high temperature spin crossover (SCO) between 360 and 500 K. Magneto-structural relationship studies reveal that π-stacking, hydrogen interactions and Coulomb interactions between the [FeIII(HATD)2]- anion and the [FeII(phen)3]2+ cation play a crucial role in the high temperature Fe(iii) SCO behaviour of complex 2.

A Review of Multimodal Medical Image Fusion Techniques.

The medical image fusion is the process of coalescing multiple images from multiple imaging modalities to obtain a fused image with a large amount of information for increasing the clinical applicability of medical images. In this paper, we attempt to give an overview of multimodal medical image fusion methods, putting emphasis on the most recent advances in the domain based on (1) the current fusion methods, including based on deep learning, (2) imaging modalities of medical image fusion, and (3) performance analysis of medical image fusion on mainly data set. Finally, the conclusion of this paper is that the current multimodal medical image fusion research results are more significant and the development trend is on the rise but with many challenges in the research field.

In vitro and in vivo biocompatibility and inflammation response of methacrylated and maleated hyaluronic acid for wound healing.

Over the past few years, different in vitro and in vivo studies have been highlighting the great potentiality of hyaluronic acid (HA) as a biomaterial in wound healing treatment thanks to its good capability to induce mesenchymal and epithelial cell growth and differentiation, angiogenesis, and collagen deposition. However, the need to improve its mechanical properties as well as its residence time has led scientists to study new functionalization strategies. In this work, chemically modified HA-based hydrogels were obtained by methacrylic and maleic functionalization. Methacrylated (MEHA) and maleated HA (MAHA) hydrogels have shown important physico-chemical properties. The present study provides a deeper insight into the biocompatibility of both synthesized materials and their effects on tissue inflammation using in vitro and in vivo models. To this aim, different cell lines involved in wound healing, human dermal fibroblasts, human adipose-derived stem cells and human umbilical vein endothelial cells, were seeded on MEHA and MAHA hydrogels. Furthermore, an inflammation study was carried out on a murine macrophage cell line to assess the effects of both hydrogels on inflammatory and anti-inflammatory interleukin production. The results showed that both MAHA and MEHA supported cell proliferation with anti-inflammation ability as highlighted by the increased levels of IL-10 (57.92 ± 9.87 pg mL-1 and 68.08 ± 13.94 pg mL-1, for MEHA and MAHA, respectively). To investigate the inflammatory response at tissue/implant interfaces, an in vivo study was also performed by subcutaneous implantation of the materials in BALB/c mice for up to 28 days. In these analyses, no significant chronic inflammation reaction was demonstrated in either MEHA or MAHA in the long-term implantation.

Role of the physical fitness test in risk prediction of diabetes among municipal in-service personnel in Guangxi.

To explore the relationship between risk prediction of diabetes mellitus (DM) and different physical fitness parameters in municipal in-service personnel in Guangxi.This was a cross-sectional study conducted in China from July 2015 to December 2016. We enrolled in-service adults (20-65 year of age) from public institutions. All subjects underwent National Physical Fitness Test (NPFT) and EZSCAN screening.The 5668 subjects were 42.9±12.3 years; 2984 (52.6%) were male; 3998 (70.5%), 1579 (27.9%) and 85 (1.6%) were Han, Zhuang, and other ethnicities, respectively. The multivariable analysis showed that systolic blood pressure (odds ratio [OR] = 1.013, 95% confidence interval [CI]: 1.003-1.022, P = .01), Harvard step test index (OR = 0.958, 95% CI: 0.941-0.976, P <.001), bend-ahead in sitting (OR = 0.945, 95% CI: 0.926-0.963, P <.001), hand grip strength (OR = 0.981, 95% CI: 0.966-0.997, P = .02), vertical jump height (OR = 0.969, 95% CI: 0.944-0.996, P = .02), time of single-leg standing with eyes closed (OR = 0.981, 95% CI: 0.968-0.995, P = .007), choice reaction time (OR = 2.103, 95% CI: 1.261-3.507, P = .004), and body composition minerals (OR = 1.649, 95% CI: 1.261-1.813, P < .001) were independently associated with DM. The resulting equation for the prediction of DM had an area under the receiver operating characteristic curve of 0.808, indicating good predictive ability.NPFT and EZSCAN could help predict the risk of diabetes and give early warnings to undertake preventive actions such as changing diet and performing physical activity.