Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung ...cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 g/kg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MS/MS. The results showed that CJ significantly increased the Cmax and AUC0-t of gefitinib by 28% and 55%, respectively. Mechanism studies indicated that CJ activated P-gp, and cranberry metabolites (CM) inhibited CYP2D6. Moreover, the protein level of P-gp in rat enterocytes was decreased, whereas that in hepatocytes was increased. In addition, the protein levels of BCRP, CYP3A4 and CYP2D6 in enterocytes and hepatocytes were decreased. In conclusion, CJ ingestion affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.
Abstract
Van der Waals heterobilayers of transition metal dichalcogenides with spin–valley coupling of carriers in different layers have emerged as a new platform for exploring spin/valleytronic ...applications. The interlayer coupling was predicted to exhibit subtle changes with the interlayer atomic registry. Manually stacked heterobilayers, however, are incommensurate with the inevitable interlayer twist and/or lattice mismatch, where the properties associated with atomic registry are difficult to access by optical means. Here, we unveil the distinct polarization properties of valley-specific interlayer excitons using epitaxially grown, commensurate WSe
2
/MoSe
2
heterobilayers with well-defined (AA and AB) atomic registry. We observe circularly polarized photoluminescence from interlayer excitons, but with a helicity opposite to the optical excitation. The negative circular polarization arises from the quantum interference imposed by interlayer atomic registry, giving rise to distinct polarization selection rules for interlayer excitons. Using selective excitation schemes, we demonstrate the optical addressability for interlayer excitons with different valley configurations and polarization helicities.
The purpose of this study is to evaluate the feasibility and patient acceptability of a novel artificial intelligence (AI)-based diabetic retinopathy (DR) screening model within endocrinology ...outpatient settings. Adults with diabetes were recruited from two urban endocrinology outpatient clinics and single-field, non-mydriatic fundus photographs were taken and graded for referable DR ( ≥ pre-proliferative DR). Each participant underwent; (1) automated screening model; where a deep learning algorithm (DLA) provided real-time reporting of results; and (2) manual model where retinal images were transferred to a retinal grading centre and manual grading outcomes were distributed to the patient within 2 weeks of assessment. Participants completed a questionnaire on the day of examination and 1-month following assessment to determine overall satisfaction and the preferred model of care. In total, 96 participants were screened for DR and the mean assessment time for automated screening was 6.9 minutes. Ninety-six percent of participants reported that they were either satisfied or very satisfied with the automated screening model and 78% reported that they preferred the automated model over manual. The sensitivity and specificity of the DLA for correct referral was 92.3% and 93.7%, respectively. AI-based DR screening in endocrinology outpatient settings appears to be feasible and well accepted by patients.
Ultraviolet (UV) radiation alone or in combination with other oxidation processes is increasingly being considered for water disinfection because of stringent regulatory requirements for pathogen ...inactivation. To fulfill this requirement, an appropriate UV dose or fluence (mJ/cm
) is applied to combat enteric viruses in surface or treated water. There is a need for a cumulative review on the effectiveness of current and emerging UV technologies against various types of human enteric viruses. We extracted the kinetics data from 52 selected experimental studies on enteric virus inactivation using low pressure (LP-UV), medium pressure (MP-UV), UV-LED, and advanced oxidation processes (AOPs) and applied a simple linear regression analysis to calculate the range of UV fluence (mJ/cm
) needed for 4-log
inactivation. The inactivation of adenoviruses with LP-UV, MP-UV, and UV/H
O
(10 mg/L) required the highest fluence, which ranged from 159 to 337, 45, and 115 mJ/cm
, respectively. By contrast, when using LP-UV, the inactivation of other enteric viruses, such as the Caliciviridae and Picornaviridae family and rotavirus, required fluence that ranged from 19 to 69, 18 to 43, and 38 mJ/cm
, respectively. ssRNA viruses exhibit higher sensitivity to UV radiation than dsRNA and DNA viruses. In general, as an upgrade to LP-UV, MP-UV is a more promising strategy for eliminating enteric viruses compared to AOP involving LP-UV with added H
O
or TiO
. The UV-LED technology showed potential because a lower UV fluence (at 260 and/or 280 nm wavelength) was required for 4-log
inactivation compared to that of LP-UV for most strains examined in this critical review. However, more studies evaluating the inactivation of enteric viruses by means of UV-LEDs and UV-AOP are needed to ascertain these observations.
Visually impaired people are often unaware of dangers in front of them, even in familiar environments. Furthermore, in unfamiliar environments, such people require guidance to reduce the risk of ...colliding with obstacles. This study proposes a simple smartphone-based guiding system for solving the navigation problems for visually impaired people and achieving obstacle avoidance to enable visually impaired people to travel smoothly from a beginning point to a destination with greater awareness of their surroundings. In this study, a computer image recognition system and smartphone application were integrated to form a simple assisted guiding system. Two operating modes, online mode and offline mode, can be chosen depending on network availability. When the system begins to operate, the smartphone captures the scene in front of the user and sends the captured images to the backend server to be processed. The backend server uses the faster region convolutional neural network algorithm or the you only look once algorithm to recognize multiple obstacles in every image, and it subsequently sends the results back to the smartphone. The results of obstacle recognition in this study reached 60%, which is sufficient for assisting visually impaired people in realizing the types and locations of obstacles around them.
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•Immobilized microbial granules improved salinity tolerance.•High ammonia removal (92%) was achieved at salinity up to 35.0 g/L.•Nitrite oxidation bacteria was depressed at salinity ...above 15.0 g/L.•Microbial community structure was shifted as salinity increased.•Nitrosomonas sp. and Nitrospira sp. were the dominant genera.
The novel immobilized microbial granules (IMG) shows a significant effect of nitrification for freshwater aquaculture. However, there is lack of evaluation study on the performance of nitrification at high salinity due to the concentration of recycled water or seawater utilization. A laboratory scale moving bed bioreactor (MBBR) with IMG was tested on recycled synthetic aquaculture wastewater for the nitrification at 2.5 mg/L NH3-N daily. The results indicated that IMG showed a high salinity tolerance and effectively converted ammonia to nitrate up to 92% at high salinity of 35.0 g/L NaCl. As salinity increased from near zero to 35.0 g/L, the microbial activity of nitrite oxidation bacteria (NOB) in the IMG decreased by 86.32%. The microbial community analysis indicated that salinity significantly influenced the community structure. It was found that Nitrosomonas sp. and Nitrospira sp. were the dominant genera for ammonia oxidation bacteria (AOB) and NOB respectively at different salinity levels.
Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent ...pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.
Convolutional neural networks have recently been applied to ophthalmic diseases; however, the rationale for the outputs generated by these systems is inscrutable to clinicians. A visualization tool ...is needed that would enable clinicians to understand important exposure variables in real time.
To systematically visualize the convolutional neural networks of 2 validated deep learning models for the detection of referable diabetic retinopathy (DR) and glaucomatous optic neuropathy (GON).
The GON and referable DR algorithms were previously developed and validated (holdout method) using 48 116 and 66 790 retinal photographs, respectively, derived from a third-party database (LabelMe) of deidentified photographs from various clinical settings in China. In the present cross-sectional study, a random sample of 100 true-positive photographs and all false-positive cases from each of the GON and DR validation data sets were selected. All data were collected from March to June 2017. The original color fundus images were processed using an adaptive kernel visualization technique. The images were preprocessed by applying a sliding window with a size of 28 × 28 pixels and a stride of 3 pixels to crop images into smaller subimages to produce a feature map. Threshold scales were adjusted to optimal levels for each model to generate heat maps highlighting localized landmarks on the input image. A single optometrist allocated each image to predefined categories based on the generated heat map.
Visualization regions of the fundus.
In the GON data set, 90 of 100 true-positive cases (90%; 95% CI, 82%-95%) and 15 of 22 false-positive cases (68%; 95% CI, 45%-86%) displayed heat map visualization within regions of the optic nerve head only. Lesions typically seen in cases of referable DR (exudate, hemorrhage, or vessel abnormality) were identified as the most important prognostic regions in 96 of 100 true-positive DR cases (96%; 95% CI, 90%-99%). In 39 of 46 false-positive DR cases (85%; 95% CI, 71%-94%), the heat map displayed visualization of nontraditional fundus regions with or without retinal venules.
These findings suggest that this visualization method can highlight traditional regions in disease diagnosis, substantiating the validity of the deep learning models investigated. This visualization technique may promote the clinical adoption of these models.
Cancer stem cell (CSC) theory has drawn much attention, with evidence supporting the contribution of stem cells to tumor initiation, relapse, and therapy resistance.
To screen drugs that target CSCs ...to improve the current treatment outcome and overcome drug resistance in patients with lung cancer.
We used publicly available embryonic stem cell and CSC-associated gene signatures to query the Connectivity Map for potential drugs that can, at least in part, reverse the gene expression profile of CSCs. High scores were noted for several phenothiazine-like antipsychotic drugs, including trifluoperazine. We then treated lung CSCs with different EGFR mutation status with trifluoperazine to examine its anti-CSC properties. Lung CSCs resistant to epidermal growth factor receptor-tyrosine kinase inhibitor or cisplatin were treated with trifluoperazine plus gefitinib or trifluoperazine plus cisplatin. Animal models were used for in vivo validation of the anti-CSC effect and synergistic effect of trifluoperazine with gefitinib.
We demonstrated that trifluoperazine inhibited CSC tumor spheroid formation and down-regulated the expression of CSC markers (CD44/CD133). Trifluoperazine inhibited Wnt/β-catenin signaling in gefitinib-resistant lung cancer spheroids. The combination of trifluoperazine with either gefitinib or cisplatin overcame drug resistance in lung CSCs. Trifluoperazine inhibited the tumor growth and enhanced the inhibitory activity of gefitinib in lung cancer metastatic and orthotopic CSC animal models.
Using in silico drug screening by Connectivity Map followed by empirical validations, we repurposed an existing phenothiazine-like antipsychotic drug, trifluoperazine, as a potential anti-CSC agent that could overcome epidermal growth factor receptor-tyrosine kinase inhibitor and chemotherapy resistance.
Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. ...Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1β, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds—adenosine and N6-(2-hydroxyethyl) adenosine (HEA)—inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.
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