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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The AKT pathway is often activated in HCC cases, and a longer exposure to tyrosine kinase inhibitors such as sorafenib may lead to over-activation of the AKT pathway, leading to HCC resistance. Here, we studied the efficacy of a new generation of allosteric AKT inhibitor, vevorisertib, alone or in combination with sorafenib. To identify specific adverse effects related to the background of cirrhosis, we used a diethylnitrosamine (DEN)-induced cirrhotic rat model. Vevorisertib was tested in vitro on Hep3B, HepG2, HuH7 and PLC/PRF cell lines. Rats were treated weekly with intra-peritoneal injections of DEN for 14 weeks to obtain cirrhosis with fully developed HCC. After that, rats were randomized into four groups (n = 7/group): control, sorafenib, vevorisertib and the combination of vevorisertib + sorafenib, and treated for 6 weeks. Tumor progression was followed by MRI. We demonstrated that the vevorisertib is a highly potent treatment, blocking the phosphorylation of AKT. The tumor progression in the rat liver was significantly reduced by treatment with vevorisertib + sorafenib (49.4%) compared to the control group (158.8%, p < 0.0001). Tumor size, tumor number and tumor cell proliferation were significantly reduced in both the vevorisertib group and vevorisertib + sorafenib groups compared to the control group. Sirius red staining showed an improvement in liver fibrosis by vevorisertib and the combination treatment. Moreover, vevorisertib + sorafenib treatment was associated with a normalization in the liver vasculature. Altogether, vevorisertib as a single agent and its combination with sorafenib exerted a strong suppression of tumor progression and improved liver fibrosis. Thus, results provide a rationale for testing vevorisertib in clinical settings and confirm the importance of targeting AKT in HCC. [ABSTRACT FROM AUTHOR]

In the field of humidity sensors, a major challenge is how to improve the sensing performance of existing materials. Based on our previous work on Na0.5Bi0.5TiO3, a facile strategy of tuning the Bi content in the material was proposed to improve its sensing performance. Na0.5BixTiO3 (x = 0.3, 0.35, 0.4, 0.45) nanocomposites were synthesized by a hydrothermal method. Humidity sensing properties of these nanocomposites were investigated in the relative humidity range of 11% to 95%. Our results show that, compared to the sensor based on nominally pure sample (Na0.5Bi0.5TiO3), the sensor based on Na0.5Bi0.35TiO3 exhibits boosted sensing performance of excellent linear humidity response in the humidity range of 11–75% relative humidity, lower hysteresis value, and faster response/recovery time. The improvement of the sensing performance was argued to be the reason that the proper reduction in Bi content leads to a minimum value of oxygen-vacancy concentrations, thereby weakening the chemical adsorption but enhancing the physical adsorption. These results indicate that the proper underdose of the Bi content in Na0.5Bi0.5TiO3 can greatly boost the sensing performance. [ABSTRACT FROM AUTHOR]

Multiple upwelling systems develop in the Indian Ocean during the summer monsoon. The Sri Lanka dome (SLD), which occurs in the open ocean off the east coast of Sri Lanka from June to September, is distinct from those near the coast. The SLD is characterized by uplifted thermocline and increased chlorophyll concentration. Mechanisms of the upwelling and its biogeochemical response are not well understood. Here, we explored the dynamics of the chlorophyll and sea-to-air CO2 flux in the SLD using ocean color and altimetry remote sensing data, together with other reanalysis products. We found that the occurrence of high chlorophyll concentration and sea-to-air CO2 flux happens along the pathway of the southwest monsoon current (SMC). The annual cycle of chlorophyll in the SLD has a one-month lag relative to that in the southern coast of Sri Lanka. The positive wind stress curl that forms in the SLD during the summer does not fully explain the seasonal chlorophyll maximum. Transport of the SMC, eddy activity, and associated frontal processes also play an important role in regulating the variability in chlorophyll. In the SLD, upwelled subsurface water has excess dissolved inorganic carbon (DIC) relative to the conventional Redfield ratio between DIC and nutrients; thus, upwelling and sub-mesoscale processes determine this region to be a net carbon source to the atmosphere. [ABSTRACT FROM AUTHOR]

Two new glucosides, salviadigitoside A (1) and salviatalin A-19-O-β-glucoside (2), belonging to the salviatalin type diterpenoids, and a new cyclopenta[c]pyridine, salviadiginine A (3), were isolated from the roots of Salvia digitaloids. Structures of these compounds were determined on the basis of spectroscopic analysis. In addition, compounds 1-3 were evaluated for their anti-inflammatory activity, but the results showed a weak anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Molecular latent representations, derived from autoencoders (AEs), have been widely used for drug or material discovery over the past couple of years. In particular, a variety of machine learning methods based on latent representations have shown excellent performance on quantitative structure–activity relationship (QSAR) modeling. However, the sequence feature of them has not been considered in most cases. In addition, data scarcity is still the main obstacle for deep learning strategies, especially for bioactivity datasets. In this study, we propose the convolutional recurrent neural network and transfer learning (CRNNTL) method inspired by the applications of polyphonic sound detection and electrocardiogram classification. Our model takes advantage of both convolutional and recurrent neural networks for feature extraction, as well as the data augmentation method. According to QSAR modeling on 27 datasets, CRNNTL can outperform or compete with state-of-art methods in both drug and material properties. In addition, the performances on one isomers-based dataset indicate that its excellent performance results from the improved ability in global feature extraction when the ability of the local one is maintained. Then, the transfer learning results show that CRNNTL can overcome data scarcity when choosing relative source datasets. Finally, the high versatility of our model is shown by using different latent representations as inputs from other types of AEs. [ABSTRACT FROM AUTHOR]

In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1). Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13) and [6]-shogaol (17) exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15) inhibited the Ca2+-dependent contractions in high K+ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism. [ABSTRACT FROM AUTHOR]

Sixteen years of satellite observational data in the Northwestern Pacific Ocean are used to describe the variability in the sea surface temperature (SST) gradient and its impact on chlorophyll-a concentrations (Chl-a). Spatially, a meridional dependence is identified in which the SST gradient increases to the north in association with elevated Chl-a. Temporally, the seasonal variability shows a large SST gradient and high Chl-a in winter and spring, while the SST gradient and Chl-a are much lower in summer. The seasonal variability in Chl-a leads the variability in the SST gradient by one month. A significant correlation between the SST gradient and Chl-a in the anomalous field is obtained only in the western section of the Kuroshio extension (KE) and the highest correlation is identified without any lags. An index for the section is defined as the proportion of the number of times that the SST gradient magnitude is anomalously large in each year, and the index is highly related to the stability of the KE and has a prominent influence on Chl-a in the region. An anomalously large positive (negative) SST gradient magnitude occurs when the KE is unstable (stable) and the corresponding Chl-a is high (low). [ABSTRACT FROM AUTHOR]

Nonsense mutations often result from single nucleotide substitutions that change a sense codon (coding for an amino acid) to a nonsense or premature termination codon (PTC) within the coding region of a gene. The impact of nonsense mutations is two-fold: (1) the PTC-containing mRNA is degraded by a surveillance pathway called nonsense-mediated mRNA decay (NMD) and (2) protein translation stops prematurely at the PTC codon, and thus no functional full-length protein is produced. As such, nonsense mutations result in a large number of human diseases. Nonsense suppression is a strategy that aims to correct the defects of hundreds of genetic disorders and reverse disease phenotypes and conditions. While most clinical trials have been performed with small molecules, there is an increasing need for sequence-specific repair approaches that are safer and adaptable to personalized medicine. Here, we discuss recent advances in both conventional strategies as well as new technologies. Several of these will soon be tested in clinical trials as nonsense therapies, even if they still have some limitations and challenges to overcome. [ABSTRACT FROM AUTHOR]

Physical layer key generation (PKG) has become a research focus as it solves the key distribution problem, which is difficult in traditional cryptographic mechanisms. Information reconciliation is a critical process in PKG to obtain symmetric keys. Various reconciliation schemes have been proposed, including the error detection protocol-based approach (EDPA) and error correction code-based approach (ECCA). Both EDPA and ECCA have advantages and drawbacks, regarding information leakage, interaction delay, and computation complexity. In this paper, we choose the BBBSS protocol from EDPA and BCH code from ECCA as a case study, analyzing their comprehensive efficiency performance versus pass number and bit disagreement ratio (BDR), respectively. Next, we integrate the strength of the two to design a new hybrid information reconciliation protocol (HIRP). The design of HIRP consists of three main phases, i.e., training, table lookup, and testing. To comprehensively evaluate the reconciliation schemes, we propose a novel efficiency metric to achieve a balance of corrected bits, information leakage, time delay, and computation time, which represents the effectively corrected bits per unit time. The simulation results show that our proposed method outperforms other reconciliation schemes to improve the comprehensive reconciliation efficiency. The average improvement in efficiency is 2.48 and 22.36 times over the BBBSS and BCH code, respectively, when the range of the BDR is from 0.5% to 11.5%. Compared to the BBBSS protocol and the BCH code, HIRP lies at a mid-level in terms of information leakage and computation time cost. Besides, with the lowest time delay cost, HIRP reaches the highest reconciliation efficiency. [ABSTRACT FROM AUTHOR]

Soil salinity is one of the most significant abiotic stresses affecting crop yield around the world. To explore the molecular mechanism of salt tolerance in rapeseed (Brassica napus L.), the transcriptome analysis and metabolomics analysis were used to dissect the differentially expressed genes and metabolites in two rapeseed varieties with significant differences in salt tolerance; one is an elite rapeseed cultivar, Huayouza 62. A total of 103 key differentially expressed metabolites (DEMs) and 53 key differentials expressed genes (DEGs) that might be related to salt stress were identified through metabolomics and transcriptomics analysis. GO and KEGG analysis revealed that the DEGs were mainly involved in ion transport, reactive oxygen scavenging, osmotic regulation substance synthesis, and macromolecular protein synthesis. The DEMs were involved in TCA cycle, proline metabolism, inositol metabolism, carbohydrate metabolic processes, and oxidation-reduction processes. In addition, overexpression of BnLTP3, which was one of the key DEGs, could increase tolerance to salt stress in Arabidopsis plants. This study reveals that the regulation mechanism of salt tolerance in rapeseed at the transcriptome and metabolism level and provides abundant data for further in-depth identification of essential salt tolerance genes. [ABSTRACT FROM AUTHOR]

The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads. [ABSTRACT FROM AUTHOR]

Background: Femoral head fractures are rare injuries with or without traumatic dislocations. The management of these fractures is crucial to prevent the development of severe complications and to achieve optimal functional outcomes. Wide treatment options for Pipkin 1 femoral head fractures range from fragment excision, fixation following open reduction with internal fixation, or conservative treatment such as close reduction alone after fracture dislocation. However, the best decision making remains controversial not only due to lack of large trials, but also inconsistent results reported. Therefore, we aim to compare the operative with nonoperative outcomes of Pipkin type 1 patients. Patients and Methods: We systemically searched MEDLINE, EMBASE, Cochrane library, In-Process & Other Non-Indexed Citations to identify studies assessing outcomes of Pipkin type 1 patients after conservative treatment, and open reduction with excision or fixation. Data on comparison of clinical outcomes of each management were extracted including arthritis, heterotopic ossification (HO), avascular necrosis (AVN), and functional scores (Thompson Epstein, Merle' d Augine and Postel Score). We performed a meta-analysis with the available data. Results: Eight studies (7 case series and 1 RCT) were included in this study. In a pooled analysis, the overall rate of arthritis was 37% (95% CI, 2–79%), HO was 20% (95% CI, 2–45%), and AVN was 3% (95% CI, 0–16%). In comparison of management types, the excision group reached the best functional outcomes including Thompson Epstein Score (poor to worse, 9%; 95% CI, 0–27%) and Merle d' Aubigne and Postel Score (poor to worse, 18%; 95% CI, 3–38%); ORIF group had the highest AVN rate (11%; 95% CI, 0–92%); conservative treatment had the highest arthritis rate (67%; 95% CI: 0–100%) and lowest HO rate (2%; 95% CI, 0–28%). Discussion: This meta-analysis demonstrates that different procedures lead to various clinical outcomes: fragment excision may achieve better function, conservative treatment may result in a higher arthritis rate, while ORIFs may have a higher AVN rate. These findings may assist surgeons in tailoring their decision-making to specific patient profiles. Future RCTs with multicenter efforts are needed to validate associations found in this study. Level of Evidence: II, systematic review and meta-analysis. [ABSTRACT FROM AUTHOR]

Photonic crystal cavities enable strong light–matter interactions, with numerous applications, such as ultra-small and energy-efficient semiconductor lasers, enhanced nonlinearities and single-photon sources. This paper reviews the properties of the modes of photonic crystal cavities, with a special focus on line-defect cavities. In particular, it is shown how the fundamental resonant mode in line-defect cavities gradually turns from Fabry–Perot-like to distributed-feedback-like with increasing cavity size. This peculiar behavior is directly traced back to the properties of the guided Bloch modes. Photonic crystal cavities based on Fano interference are also covered. This type of cavity is realized through coupling of a line-defect waveguide with an adjacent nanocavity, with applications to Fano lasers and optical switches. Finally, emerging cavities for extreme dielectric confinement are covered. These cavities promise extremely strong light–matter interactions by realizing deep sub-wavelength mode size while keeping a high quality factor. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the whole plants of Andrographis echioides afforded two new 2'-oxygenated flavonoids (1) and (2), two new phenyl glycosides (3) and (4), along with 37 known structures. The structures of new compounds were elucidated by spectral analysis and chemical transformation studies. Among the isolated compounds, (1-2) and (6-19) were subjected into the examination for their iNOS inhibitory bioactivity. The structure-activity relationships of the flavonoids for their inhibition of NO production were also discussed. [ABSTRACT FROM AUTHOR]

Operational monsoon moisture surveillance and severe weather prediction is essential for timely water resource management and disaster risk reduction. For these purposes, this study suggests a moisture indicator using the COSMIC-2/FORMOSAT-7 radio occultation (RO) observations and evaluates numerical model experiments with RO data assimilation. The RO data quality is validated by a comparison between sampled RO profiles and nearby radiosonde profiles around Taiwan prior to the experiments. The suggested moisture indicator accurately monitors daily moisture variations in the South China Sea and the Bay of Bengal throughout the 2020 monsoon rainy season. For the numerical model experiments, the statistics of 152 moisture and rainfall forecasts for the 2020 Meiyu season in Taiwan show a neutral to slightly positive impact brought by RO data assimilation. A forecast sample with the most significant improvement reveals that both thermodynamic and dynamic fields are appropriately adjusted by model integration posterior to data assimilation. The statistics of 17 track forecasts for typhoon Hagupit (2020) also show the positive effect of RO data assimilation. A forecast sample reveals that the member with RO data assimilation simulates better typhoon structure and intensity than the member without, and the effect can be larger and faster via multi-cycle RO data assimilation. [ABSTRACT FROM AUTHOR]

Simple Summary: Imatinib mesylate (IM, Gleevec) has remained first-line therapy for most gastrointestinal stromal tumor (GIST) patients since 2002. During this time, three additional inhibitors have been approved for treatment of IM-refractory tumors; however, disease stabilization for these agents is measured in months. Once all approved lines of therapy are ineffective, patients with advanced GIST are left without treatment options. Therefore, preventing or delaying development of acquired resistance to IM could have clinical benefits. Activation of the PI3K/AKT signaling pathway has been associated with resistance to IM in GIST. We evaluated MK-4440, a novel AKT inhibitor, in combination with IM in GIST cells and mouse models. Our studies demonstrate superior activity of MK-4440/IM combination in a panel of GIST cell lines caused by cell cycle arrest and elevated PDCD4 expression leading to increased cell death. Furthermore, dual inhibition of KIT and AKT provided impressive disease stabilization in IM-sensitive GIST growing in mice. The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. In addition to KIT, AKT is a relevant target for inhibition, since the PI3K/AKT pathway is crucial for IM-resistant GIST survival. We evaluated the activity of a novel pan-AKT inhibitor, MK-4440 (formerly ARQ 751), as monotherapy and in combination with IM in GIST cell lines and preclinical models with varying IM sensitivities. Dual inhibition of KIT and AKT demonstrated synergistic effects in IM-sensitive and -resistant GIST cell lines. Proteomic analyses revealed upregulation of the tumor suppressor, PDCD4, in combination treated cells. Enhanced PDCD4 expression correlated to increased cell death. In vivo studies revealed superior efficacy of MK-4440/IM combination in an IM-sensitive preclinical model of GIST compared with either single agent. The combination demonstrated limited efficacy in two IM-resistant models, including a GIST patient-derived xenograft model possessing an exon 9 KIT mutation. These studies provide strong rationale for further use of AKT inhibition in combination with IM in primary GIST; however, alternative agents will need to be tested in combination with AKT inhibition in the resistant setting. [ABSTRACT FROM AUTHOR]

The Model for Prediction Across Scales (MPAS) is used to simulate the East Asian winter monsoon (EAWM) over the 2011–2020 winter. The 45 day hindcasts are made with 30 km horizontal resolution and constructed to a time-lagged ensemble system. The climatology, the major modes of EAWM variability, and the blocking activities are examined. The evaluation results reveal that MPAS can simulate the climatologic characteristics of EAWM reasonably, with a surface cold bias of 4% and a positive rainfall bias of 9% over East Asia. MPAS can perform skillfully in the forecasts of surface temperature probability of East Asia and is more reliable in detecting below normal and above normal events. The features that influence the EAWM variability are also analyzed. MPAS simulates reasonably in the occurrence frequency of blocking high in both locations and duration time. The empirical orthogonal function analysis also shows that MPAS can capture the two major modes of the surface temperature of EAWM. On the other hand, it is also found that a biased sea surface temperature may modify the circulations over the Western Pacific and affect the simulated occurrence frequency of cold events near Taiwan during winter. [ABSTRACT FROM AUTHOR]

A highly specific and sensitive proton nuclear magnetic resonance (1H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra-related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved. [ABSTRACT FROM AUTHOR]

Highly accurate and precise heave decay tests on a sphere with a diameter of 300 mm were completed in a meticulously designed test setup in the wave basin in the Ocean and Coastal Engineering Laboratory at Aalborg University, Denmark. The tests were dedicated to providing a rigorous benchmark dataset for numerical model validation. The sphere was ballasted to half submergence, thereby floating with the waterline at the equator when at rest in calm water. Heave decay tests were conducted, wherein the sphere was held stationary and dropped from three drop heights: a small drop height, which can be considered a linear case, a moderately nonlinear case, and a highly nonlinear case with a drop height from a position where the whole sphere was initially above the water. The precision of the heave decay time series was calculated from random and systematic standard uncertainties. At a 95% confidence level, uncertainties were found to be very low—on average only about 0.3% of the respective drop heights. Physical parameters of the test setup and associated uncertainties were quantified. A test case was formulated that closely represents the physical tests, enabling the reader to do his/her own numerical tests. The paper includes a comparison of the physical test results to the results from several independent numerical models based on linear potential flow, fully nonlinear potential flow, and the Reynolds-averaged Navier–Stokes (RANS) equations. A high correlation between physical and numerical test results is shown. The physical test results are very suitable for numerical model validation and are public as a benchmark dataset. [ABSTRACT FROM AUTHOR]

The development of multidrug resistance (MDR) in cancer patients, which is often associated with the overexpression of ABCB1 (MDR1, P-glycoprotein) in cancer cells, remains a significant problem in cancer chemotherapy. ABCB1 is one of the major adenosine triphosphate (ATP)-binding cassette (ABC) transporters that can actively efflux a range of anticancer drugs out of cancer cells, causing MDR. Given the lack of Food and Drug Administration (FDA)-approved treatment for multidrug-resistant cancers, we explored the prospect of repurposing erdafitinib, the first fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA, to reverse MDR mediated by ABCB1. We discovered that by reducing the function of ABCB1, erdafitinib significantly resensitized ABCB1-overexpressing multidrug-resistant cancer cells to therapeutic drugs at sub-toxic concentrations. Results of erdafitinib-stimulated ABCB1 ATPase activity and in silico docking analysis of erdafitinib binding to the substrate-binding pocket of ABCB1 further support the interaction between erdafitinib and ABCB1. Moreover, our data suggest that ABCB1 is not a major mechanism of resistance to erdafitinib in cancer cells. In conclusion, we revealed an additional action of erdafitinib as a potential treatment option for multidrug-resistant cancers, which should be evaluated in future drug combination trials. [ABSTRACT FROM AUTHOR]

Organic–inorganic halide perovskites are promising photovoltaic materials with excellent optoelectronic properties. However, the extreme structural instability hinders their wide application as well as the microstructure characterization using high energy beams such as transmission electron microscopy (TEM). Here, taking BA2FAPb2I7 and BA2MAPb2I7 as examples, we investigate their structural evolution resulting from high energy electron irradiation, moist air, and low temperature, respectively. The results show that the long organic chains are the first to be damaged under electron beam, which is mainly arising from their instability and weak bonding with the framework of [PbI6]4− octahedrons. Then the short organic cations and the framework of [PbI6]4− octahedrons collapses gradually. The final products are clusters of detached PbI2 particles, which can also be observed in the sample degraded in moist air. In addition, the structures of BA2FAPb2I7 and BA2MAPb2I7 are discovered to undergo a phase transformation at liquid nitrogen temperature, which calls attention to the community that cryo-TEM methods should be used cautiously for organic–inorganic halide perovskite materials. [ABSTRACT FROM AUTHOR]

The development of multidrug resistance (MDR) in cancer patients driven by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells presents one of the most daunting therapeutic complications for clinical scientists to resolve. Despite many novel therapeutic strategies that have been tested over the years, there is still no approved treatment for multidrug-resistant cancers to date. We have recently adopted a drug repurposing approach to identify therapeutic agents that are clinically active and at the same time, capable of reversing multidrug resistance mediated by ABCB1 and ABCG2. In the present study, we investigated the effect of sitravatinib, a novel multitargeted receptor tyrosine kinase inhibitor, on human ABCB1 and ABCG2 in multidrug-resistant cancer cell lines. We discovered that at submicromolar concentrations, sitravatinib re-sensitizes ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. We found that sitravatinib blocks the drug efflux function of ABCB1 and ABCG2 in a concentration-dependent manner but does not significantly alter the protein expression of ABCB1 or ABCG2 in multidrug-resistant cancer cells. In conclusion, we reveal a potential drug repositioning treatment option for multidrug-resistant cancers by targeting ABCB1 and ABCG2 with sitravatinib and should be further investigated in future clinical trials. [ABSTRACT FROM AUTHOR]

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections. [ABSTRACT FROM AUTHOR]

The nectarine is an important fruit, which is attacked by Drosophila suzukii in Europe and the United States but there are no reports of it attacking nectarines in China. Here, we determined the oviposition preference of D. suzukii six on intact and sliced nectarine varieties in China and how physical and physiological indexes of the fruit correlate with these preferences. D. suzukii were allowed to oviposit on two early–, two middle– and two late–maturing varieties of nectarine—Shuguang and Chunguang, Fengguang and Zhong you 4, Zhong you 7 and Zhong you 8, respectively and the number of larvae also followed the order. The firmness, soluble solids content and the nutritional components of the amino acid, protein, soluble sugar and pectin contents of each variety were measured. D. suzukii preferred the early Shuguang variety, followed by the early Chunguang variety and then the middle Zhong you 4 and Fengguang varieties. Taken together, results show that D. suzukii shows preferences for earlier rather than later varieties of nectarines in China and that these preferences are related to the fruit's physical and physiological traits. Results suggest that mixed cultivation of early–, middle– and late–maturing nectarine varieties should be avoided in order to prevent fly dispersal and infestation by D. suzukii. [ABSTRACT FROM AUTHOR]

The strong strain-mediated magnetoelectric (ME) coupling found in thin-film ME heterostructures has attracted an ever-increasing interest and enables realization of a great number of integrated multiferroic devices, such as magnetometers, mechanical antennas, RF tunable inductors and filters. This paper first reviews the thin-film characterization techniques for both piezoelectric and magnetostrictive thin films, which are crucial in determining the strength of the ME coupling. After that, the most recent progress on various integrated multiferroic devices based on thin-film ME heterostructures are presented. In particular, rapid development of thin-film ME magnetometers has been seen over the past few years. These ultra-sensitive magnetometers exhibit extremely low limit of detection (sub-pT/Hz1/2) for low-frequency AC magnetic fields, making them potential candidates for applications of medical diagnostics. Other devices reviewed in this paper include acoustically actuated nanomechanical ME antennas with miniaturized size by 1–2 orders compared to the conventional antenna; integrated RF tunable inductors with a wide operation frequency range; integrated RF tunable bandpass filter with dual H- and E-field tunability. All these integrated multiferroic devices are compact, lightweight, power-efficient, and potentially integrable with current complementary metal oxide semiconductor (CMOS) technology, showing great promise for applications in future biomedical, wireless communication, and reconfigurable electronic systems. [ABSTRACT FROM AUTHOR]

Previous study has demonstrated that the riboflavin treatment promoted the early ripening of the 'Kyoho' grape berry. However, the molecular mechanism causing this was unclear. In order to reveal the regulation mechanism of riboflavin treatment on grape berry development and ripening, the different berry developmental stages of the 'Kyoho' berry treated with 0.5 mmol/L of riboflavin was sampled for transcriptome profiling. RNA-seq revealed that 1526 and 430 genes were up-regulated and down-regulated, respectively, for the comparisons of the treatment to the control. TCseq analysis showed that the expression patterns of most of the genes were similar between the treatment and the control, except for some genes that were related to the chlorophyll metabolism, photosynthesis–antenna proteins, and photosynthesis, which were revealed by the enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The differentially expressed genes and weighted gene co-expression network analysis (WGCNA) analysis identified some significantly differentially expressed genes and some hub genes, including up-regulation of the photosynthesis-related ELIP1 and growth and development-related GDSL; and down-regulation of the oxidative stress-related ATHSP22 and berry softening-related XTH32 and GH9B15. The results suggested that the riboflavin treatment resulted in the variations of the expression levels of these genes, and then led to the early ripening of the 'Kyoho' berry. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) causes superficial infections such as cellulitis or invasive infections such as osteomyelitis; however, differences in MRSA isolates from cellulitis (CL-MRSA) and from osteomyelitis (OM-MRSA) at the same local area remain largely unknown. A total of 221 MRSA isolates including 106 CL-MRSA strains and 115 OM-MRSA strains were collected at Chang-Gung Memorial Hospital in Taiwan between 2016 and 2018, and their genotypic and phenotypic characteristics were compared. We found that OM-MRSA isolates significantly exhibited higher rates of resistance to multiple antibiotics than CL-MRSA isolates. Genotypically, OM-MRSA isolates had higher proportions of the SCCmec type III, the sequence type ST239, and the spa type t037 than CL-MRSA isolates. Besides the multidrug-resistant lineage ST239-t037-SCCmecIII more prevalent in OM-MRSA, higher antibiotic resistance rates were also observed in several other prevalent lineages in OM-MRSA as compared to the same lineages in CL-MRSA. Furthermore, when prosthetic joint infection (PJI) associated and non-PJI-associated MRSA strains in osteomyelitis were compared, no significant differences were observed in antibiotic resistance rates between the two groups, albeit more diverse genotypes were found in non-PJI-associated MRSA. Our findings therefore suggest that deep infections may allow MRSA to evade antibiotic attack and facilitate the convergent evolution and selection of multidrug-resistant lineages. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN) is an estrogenic mycotoxin which can cause loss in animal production. The aim of this study was to screen Bacillus strains for their ZEN detoxification capability and use a fermentation process to validate their potential application in the feed industry. In the high-level ZEN-contaminated maize (5 mg·kg−1) fermentation test, B2 strain exhibited the highest detoxification rate, removing 56% of the ZEN. However, B2 strain was not the strain with the highest ZEN detoxification in the culturing media. When B2 grew in TSB medium with ZEN, it had higher bacterial numbers, lactic acid, acetic acid, total volatile fatty acids, and ammonia nitrogen. The ZEN-contaminated maize fermented by B2 strain had better fermentation characteristics (lactic acid > 110 mmol·L−1; acetic acid < 20 mmol·L−1; pH < 4.5) than ZEN-free maize. Furthermore, B2 also had detoxification capabilities toward aflatoxins B1, deoxynivalenol, fumonisin B1, and T2 toxin. Our study demonstrated differences in screening outcome between bacterial culturing conditions and the maize fermentation process. This is important for the feed industry to consider when choosing a proper method to screen candidate isolates for the pretreatment of ZEN-contaminated maize. It appears that using the fermentation process to address the ZEN-contaminated maize problem in animal feed is a reliable choice. [ABSTRACT FROM AUTHOR]

Previous investigations proposed a link between the Epstein-Barr virus (EBV) and lung cancer (LC), but the results are highly controversial largely due to the insufficient sample size and the inherent limitation of the traditional viral screening methods such as PCR. Unlike PCR, current next-generation sequencing (NGS) utilizes an unbiased method for the global assessment of all exogenous agents within a cancer sample with high sensitivity and specificity. In our current study, we aim to resolve this long-standing controversy by utilizing our unbiased NGS-based informatics approaches in conjunction with traditional molecular methods to investigate the role of EBV in a total of 1127 LC. In situ hybridization analysis of 110 LC and 10 normal lung samples detected EBV transcripts in 3 LC samples. Comprehensive virome analyses of RNA sequencing (RNA-seq) data sets from 1017 LC and 110 paired adjacent normal lung specimens revealed EBV transcripts in three lung squamous cell carcinoma and one lung adenocarcinoma samples. In the sample with the highest EBV coverage, transcripts from the BamHI A region accounted for the majority of EBV reads. Expression of EBNA-1, LMP-1 and LMP-2 was observed. A number of viral circular RNA candidates were also detected. Thus, we for the first time revealed a type II latency-like viral transcriptome in the setting of LC in vivo. The high-level expression of viral BamHI A transcripts in LC suggests a functional role of these transcripts, likely as long non-coding RNA. Analyses of cellular gene expression and stained tissue sections indicated an increased immune cell infiltration in the sample expressing high levels of EBV transcripts compared to samples expressing low EBV transcripts. Increased level of immune checkpoint blockade factors was also detected in the sample with higher levels of EBV transcripts, indicating an induced immune tolerance. Lastly, inhibition of immune pathways and activation of oncogenic pathways were detected in the sample with high EBV transcripts compared to the EBV-low LC indicating the direct regulation of cancer pathways by EBV. Taken together, our data support the notion that EBV likely plays a pathological role in a subset of LC. [ABSTRACT FROM AUTHOR]

Various retinal vessel segmentation methods based on convolutional neural networks were proposed recently, and Dense U-net as a new semantic segmentation network was successfully applied to scene segmentation. Retinal vessel is tiny, and the features of retinal vessel can be learned effectively by the patch-based learning strategy. In this study, we proposed a new retinal vessel segmentation framework based on Dense U-net and the patch-based learning strategy. In the process of training, training patches were obtained by random extraction strategy, Dense U-net was adopted as a training network, and random transformation was used as a data augmentation strategy. In the process of testing, test images were divided into image patches, test patches were predicted by training model, and the segmentation result can be reconstructed by overlapping-patches sequential reconstruction strategy. This proposed method was applied to public datasets DRIVE and STARE, and retinal vessel segmentation was performed. Sensitivity (Se), specificity (Sp), accuracy (Acc), and area under each curve (AUC) were adopted as evaluation metrics to verify the effectiveness of proposed method. Compared with state-of-the-art methods including the unsupervised, supervised, and convolutional neural network (CNN) methods, the result demonstrated that our approach is competitive in these evaluation metrics. This method can obtain a better segmentation result than specialists, and has clinical application value. [ABSTRACT FROM AUTHOR]

Strengthening existing reinforced concrete (RC) columns using a partial wrapping strengthening technique (PWST) by fiber-reinforced polymer (FRP) strips has been widely implemented. However, compared with the confinement mechanism of confined concrete in columns strengthened with the FRP full wrapping strengthening technique (FWST), the confinement mechanism of confined concrete in FRP partially wrapped columns is less understood. This paper presents the results of an experimental investigation into the behavior of confined concrete in FRP partially wrapped square columns under axial compression. The effects of FRP strip width and thickness on stress–strain behavior were thoroughly investigated. The novel particle image velocimetry (PIV) non-contact strain sensing technique was adopted to measure the strain in the specimens. Results show that the axial strains as well as the hoop strains are generally larger at the mid-plane of adjacent FRP strips than those at the mid-plane of each FRP strip, and considerable variation in hoop strains along the height of the specimens was observed. Comparisons between the experimental results and predictions by existing design-oriented stress–strain models were carried out to examine the accuracy of the models. A new design-oriented stress–strain model is proposed for confined concrete in FRP partially wrapped square columns and the comparisons between laboratory results and predictions from the proposed model show that the proposed model is superior to the existing models. [ABSTRACT FROM AUTHOR]

In this study, we developed biodegradable lidocaine–/vancomycin–/ceftazidime–eluting poly(d,l–lactide–co–glycolide) (PLGA) nano/microparticulate carriers using an electrospraying process, and we evaluated the release behaviors of the carriers in knee joints. To prepare the particles, predetermined weight percentages of PLGA, vancomycin, ceftazidime, and lidocaine were dissolved in solvents. The PLGA/antibiotic/lidocaine solutions were then fed into a syringe for electrospraying. After electrospraying, the morphology of the sprayed nano/microparticles was elucidated by scanning electron microscopy (SEM). The in vitro antibiotic/analgesic release characteristics of the nano/microparticles were studied using high-performance liquid chromatography (HPLC). In addition, drug release to the synovial tissues and fluids was studied in vivo by injecting drug-loaded nano/microparticles into the knee joints of rabbits. The biodegradable electrosprayed nano/microparticles released high concentrations of vancomycin/ceftazidime (well above the minimum inhibition concentration) and lidocaine into the knee joints for more than 2 weeks and for over 3 days, respectively. Such results suggest that electrosprayed biodegradable nano/microcarriers could be used for the long-term local delivery of various pharmaceuticals. [ABSTRACT FROM AUTHOR]