Culex quinquefasciatus is the major vector of the bancroftian filarial parasite which causes human lymphatic filariasis and St. Louis encephalitis. The simple way to stop the transmission is to control the vector by using synthetic chemicals. However, herbal essential oils have biological properties, such as a larvicidal effect and are ecofriendly to use. In this study, we investigated the larvicidal activity of Curcuma zedoaria essential oil (ZEO) and biosynthesized silver nanoparticles using this essential oil (ZEO-AgNPs). The larvicidal activity against both insecticide-susceptible and -resistant strains of Cx. quinquefasciatus larvae of ZEO were investigated and compared with ZEO-AgNPs. The ZEO-AgNPs showed the utmost toxicity against both strains of Cx. quinquefasciatus. After 24 h of exposure, LC50 and LC99 of ZEO against susceptible strain were 36.32 and 85.11 ppm, respectively. While LC50 and LC99 of ZEO against the resistant strain were 37.29 and 76.79 ppm, respectively. Whereas ZEO-AgNPs offered complete larval mortality within 24 h of exposure, LC50 and LC99 of ZEO-AgNPs against the susceptible strain, were 0.57 and 8.54 ppm, respectively. For the resistant strain, LC50 and LC99 values were 0.64 and 8.88 ppm, respectively. The potency in killing Cx. quinquefasciatus and stability of ZEO-AgNPs have made this product a good candidate for the development of novel natural larvicides.

Background: Characterisation of molecular alterations of pleomorphic lobular carcinoma (PLC), an aggressive subtype of invasive lobular carcinoma (ILC), have not been yet completely accomplished. Methods: To investigate the molecular alterations of invasive lobular carcinoma with pleomorphic features, a total of 39 tumour samples (in situ and invasive lesions and lymph node metastases) from 27 patients with nuclear grade 3 invasive lobular carcinomas were subjected to morphological, immunohistochemical and massive parallel sequencing analyses. Results: Our observations indicated that invasive lobular carcinomas with pleomorphic features were morphologically and molecularly heterogeneous. All cases showed absence or aberrant expression of E-cadherin and abnormal expression of β-catenin and p120. CDH1 (89%), PIK3CA (33%) and ERRB2 (26%) were the most common mutated genes. ERBB2 mutations preferentially affected the tyrosine-kinase activity domain, being the most frequent the targetable mutation p.L755S (57%). We also observed higher frequency of mutations in ARID1B, KMT2C, MAP3K1, TP53 and ARID1A in PLC than previously reported in classic ILC. Alterations related to progression from in situ to invasive carcinoma and/or to lymph node metastases included TP53 mutation, amplification of PIK3CA and CCND1 and loss of ARID1A expression. Conclusions: The high frequency of ERBB2 mutations observed suggests that ERBB2 mutation testing should be considered in all invasive lobular carcinomas with nuclear grade 3.

Soil organic matter (SOM) and pH are essential soil fertility indictors of paddy soil in the middle-lower Yangtze Plain. Rapid, non-destructive and accurate determination of SOM and pH is vital to preventing soil degradation caused by inappropriate land management practices. Visible-near infrared (vis-NIR) spectroscopy with multivariate calibration can be used to effectively estimate soil properties. In this study, 523 soil samples were collected from paddy fields in the Yangtze Plain, China. Four machine learning approaches-partial least squares regression (PLSR), least squares-support vector machines (LS-SVM), extreme learning machines (ELM) and the Cubist regression model (Cubist)-were used to compare the prediction accuracy based on vis-NIR full bands and bands reduced using the genetic algorithm (GA). The coefficient of determination (R²), root mean square error (RMSE), and ratio of performance to inter-quartile distance (RPIQ) were used to assess the prediction accuracy. The ELM with GA reduced bands was the best model for SOM (SOM: R² = 0.81, RMSE = 5.17, RPIQ = 2.87) and pH (R² = 0.76, RMSE = 0.43, RPIQ = 2.15). The performance of the LS-SVM for pH prediction did not differ significantly between the model with GA (R² = 0.75, RMSE = 0.44, RPIQ = 2.08) and without GA (R² = 0.74, RMSE = 0.45, RPIQ = 2.07). Although a slight increase was observed when ELM were used for prediction of SOM and pH using reduced bands (SOM: R² = 0.81, RMSE = 5.17, RPIQ = 2.87; pH: R² = 0.76, RMSE = 0.43, RPIQ = 2.15) compared with full bands (R² = 0.81, RMSE = 5.18, RPIQ = 2.83; pH: R² = 0.76, RMSE = 0.45, RPIQ = 2.07), the number of wavelengths was greatly reduced (SOM: 201 to 44; pH: 201 to 32). Thus, the ELM coupled with reduced bands by GA is recommended for prediction of properties of paddy soil (SOM and pH) in the middle-lower Yangtze Plain.

(1) Background: Appetite loss in older people, the 'Anorexia of Aging' (AA), is common, associated with under-nutrition, sarcopenia, and frailty and yet receives little attention. This review had two aims: describe interventions for AA and their effectiveness, and identify the methods of appetite assessment. (2) Methods: Study inclusion: participants aged ≥65, intervention for AA, and appetite assessment, any design, and comparator. Exclusion: studies on specific health cohorts. Searches in four databases with hand searching of references and citing works. Two researchers independently assessed eligibility and quality. (3) Results: Authors screened 8729 titles, 46 full texts. Eighteen articles were included describing nine intervention types: education (n = 1), exercise (n = 1), flavor enhancement (n = 2), increased meal variety (n = 1), mealtime assistance (n = 1), fortified food (n = 1), oral nutritional supplement (ONS) (n = 8), amino acids (n = 1), and medication (n = 2). Three studies evaluated combinations: education + exercise, ONS + exercise, and ONS + medication. Five intervention types exhibited favorable effects on appetite but in single datasets or not replicated. Appetite was assessed predominantly by Likert (n = 9), or visual analogue scales (n = 7). (4) Conclusions: A variety of interventions and methods of appetite assessments were used. There was a lack of clarity about whether AA or undernutrition was the intervention target. AA is important for future research but needs standardized assessment so that effectiveness of a range of interventions can be fully explored.

A series of thiosemicarbazide derivatives was designed and synthesized by reaction of carboxylic acid hydrazide with isothiocyanates. The molecular structures of the investigated thiosemicarbazides were confirmed and characterized by spectroscopic analysis. The conformational preference of carbonylthiosemicarbazide chain and intra- and intermolecular interactions in the crystalline state were characterized using X-ray analysis. The antituberculosis activity of the target compounds were tested in vitro against four Mycobacterium strains: M. H37Ra, M. phlei, M. smegmatis, M. timereck. The most active compounds were those with 2-pyridine ring. They exhibited lower minimal inhibitory concentration (MIC) values in the range 7.81⁻31.25 μg/mL in comparison to the other isomers. Compound 5 had activity against M. smegmatis at a concentration of 7.81 μg/mL whereas compound 2 had activity against all tested strains at a concentration of 15.625 μg/mL. The molecular docking studies were performed for investigated compounds using the Mycobacterium tuberculosis glutamine synthetase MtGS as their molecular target.

Metronomic agents reduce the effective doses and adverse effects of cytostatics in cancer chemotherapy. Therefore, they can enhance the treatment efficiency of drug-resistant cancers. Cytostatic and anti-angiogenic effects of fenofibrate (FF) suggest that it can be used for the metronomic chemotherapy of drug-resistant prostate tumors. To estimate the effect of FF on the drug-resistance of prostate cancer cells, we compared the reactions of naïve and drug-resistant cells to the combined treatment with docetaxel (DCX)/mitoxantrone (MTX) and FF. FF sensitized drug-resistant DU145 and PC3 cells to DCX and MTX, as illustrated by their reduced viability and invasive potential observed in the presence of DCX/MTX and FF. The synergy of the cytostatic activities of both agents was accompanied by the inactivation of P-gp-dependent efflux, dysfunction of the microtubular system, and induction of polyploidy in DCX-resistant cells. Chemical inhibition of PPARα- and reactive oxygen species (ROS)-dependent pathways by GW6471 and N-acetyl-L-cysteine, respectively, had no effect on cell sensitivity to combined DCX/FF treatment. Instead, we observed the signs of adenosine triphosphate (ATP) deficit and autophagy in DCX/FF-treated drug-resistant cells. Furthermore, the cells that had been permanently propagated under DCX- and DCX/FF-induced stress did not acquire DCX/FF-resistance. Instead, relatively slow proliferation of DCX-resistant cells was efficiently inhibited by FF. Collectively, our observations show that FF reduces the effective doses of DCX by interfering with the drug resistance and energy metabolism of prostate cancer cells. Concomitantly, it impairs the chemotherapy-induced microevolution and expansion of DCX/FF-resistant cells. Therefore, FF can be applied as a metronomic agent to enhance the efficiency of palliative chemotherapy of prostate cancer.

The mechanisms behind the induction of malignancy and chemoresistance in breast cancer cells are still not completely understood. Inflammation is associated with the induction of malignancy in different types of cancer and is highlighted as an important factor for chemoresistance. In previous work, we demonstrated that the inflammatory cytokine interleukin 1β (IL-1β)-induced upregulation of genes was associated with chemoresistance in breast cancer cells. Here, we evaluated the participation and the expression profile of TP63 in the induction of resistance to cisplatin. By loss-of-function assays, we identified that IL-1β particularly upregulates the expression of the tumor protein 63 (TP63) isoform ΔNP63α, through the activation of the IL-1β/IL-1RI/β-catenin signaling pathway. Upregulation of ΔNP63α leads to an increase in the expression of the cell survival factors epidermal growth factor receptor (EGFR) and phosphatase 1D (Wip1), and a decrease in the DNA damage sensor, ataxia-telangiectasia mutated (ATM). The participation of these processes in the increase of resistance to cisplatin was confirmed by silencing TP63 expression or by inhibition of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) activity in the IL-1β/IL-1RI/β-catenin signaling pathway. These data reinforced the importance of an inflammatory environment in the induction of drug resistance in cancer cells and uncovered a molecular mechanism where the IL-1β signaling pathway potentiates the acquisition of cisplatin resistance in breast cancer cells.

Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis.

We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB in 131 HNSCC samples. Brain-derived neurotrophic factor was highly expressed in normal mucosa in HNSCC tissue and in cell lines, whereas only 42.74% of HNSCC tissue was TrkB⁺. One fourth of HNSCC cases was human papilloma virus (HPV)- positive, but the TrkB IHC frequency was not different in HPV-positive (HPV⁺) and negative cases. The UPCI-SCC090 cells expressed constitutive levels of TrkB. Transforming-growth-factor-β1 (1 ng/mL TGF-β1) induced TrkB in a subpopulation of SCC-25 cells. A single 10-µg/mL mitomycin C treatment in UPCI-SCC090 cells induced apoptosis and BDNF did not rescue them. The SCC-25 cells were resistant to the MMC treatment, and their growth decreased after TGF-β1 treatment, but was restored by BDNF if it followed TGF-β1. Taken together, BDNF might be ineffective in HPV⁺ HNSCC patients. In HPV- HNSCC patients, tumor cells did not die after chemotherapeutic challenge and BDNF with TGF-β1 could improve tumor cell survival and contribute to worse patient prognosis.

In China, public hospitals are the main provider of inpatient service. The Chinese public hospital reform has recently shifted towards health care organizations and delivery to improve health care quality. This study analyzes the variation of one of the dimensions of health care quality, patient-centeredness, among inpatients with different socioeconomic status and geographical residency in China. 1471 respondents who received inpatient care in public hospitals were included in our analysis. Patient-centeredness performance was assessed on the dimensions of Communication, Autonomy, Dignity, and Confidentiality. Variations of inpatient experience were estimated using binary logistic regression models according to: residency, region, age, gender, education, income quintile, self-rated health, and number of hospital admissions. Our results indicate that older patients, and patients living in rural areas and Eastern China are more likely to report positive experience of their public hospital stay according to the care aspects of Dignity, Communication, Confidentiality and Autonomy. However, there remains a gap between China and other countries in relation to inpatient experience. Noticeable disparities in inpatient experience also persist between different geographical regions in China. These variations of patient experience pose a challenge that China's health policy makers would need to consider in their future reform efforts.

Viability is an important quality factor influencing seed germination and crop yield. Current seed-viability testing methods rely on conventional manual inspections, which use destructive, labor-intensive and time-consuming measurements. The aim of this study is to distinguish between viable and nonviable soybean seeds, using a near-infrared (NIR) hyperspectral imaging (HSI) technique in a rapid and nondestructive manner. The data extracted from the NIR⁻HSI of viable and nonviable soybean seeds were analyzed using a partial least-squares discrimination analysis (PLS-DA) technique for classifying the viable and nonviable soybean seeds. Variable importance in projection (VIP) was used as a waveband selection method to develop a multispectral imaging model. Initially, the spectral profile of each pixel in the soybean seed images was subjected to PLS-DA analysis, which yielded a reasonable classification accuracy; however, the pixel-based classification method was not successful for high accuracy detection for nonviable seeds. Another viability detection method was then investigated: a kernel image threshold method with an optimum-detection-rate strategy. The kernel-based classification of seeds showed over 95% accuracy even when using only seven optimal wavebands selected through VIP. The results show that the proposed multispectral NIR imaging method is an effective and accurate nondestructive technique for the discrimination of soybean seed viability.

Coating ion exchange membranes with polyelectrolyte has been proven to be a cheap way to reduce concentration polarization and increase limiting current (for polyelectrolytes carrying fixed groups of the same sign of charge with respect to the membrane bulk), to create high monovalent selectivity, and to add the function of H⁺/OH- ions generation (for polyelectrolytes bearing fixed groups of the opposite sign of charge with respect to the membrane bulk). In the latter case, the balance between the counterion transport and the H⁺/OH- ions generation is affected by parameters of the substrate and the modifying layer. In this study we investigated the electrochemical characteristics of homogeneous Neosepta AMX-Sb and heterogeneous MA-41P membranes coated with one, two, or three layers of oppositely charged polyelectrolyte (the maximum thickness of each layer was 5 µm). It was found that the limiting current decreased earlier and the generation of H⁺/OH- ions was stronger in the case of the heterogeneous membrane. The shift in the pH of the solution depended more on the generation of H⁺/OH- ions at the modifying layer/solution interface than on the generation at the membrane/modifying layer interface, and in all cases water splitting started in the same range of potential drops over the membrane.

Solute carrier family 35 member A5 (SLC35A5) is a member of the SLC35A protein subfamily comprising nucleotide sugar transporters. However, the function of SLC35A5 is yet to be experimentally determined. In this study, we inactivated the SLC35A5 gene in the HepG2 cell line to study a potential role of this protein in glycosylation. Introduced modification affected neither N- nor O-glycans. There was also no influence of the gene knock-out on glycolipid synthesis. However, inactivation of the SLC35A5 gene caused a slight increase in the level of chondroitin sulfate proteoglycans. Moreover, inactivation of the SLC35A5 gene resulted in the decrease of the uridine diphosphate (UDP)-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine Golgi uptake, with no influence on the UDP-galactose transport activity. Further studies demonstrated that SLC35A5 localized exclusively to the Golgi apparatus. Careful insight into the protein sequence revealed that the C-terminus of this protein is extremely acidic and contains distinctive motifs, namely DXEE, DXD, and DXXD. Our studies show that the C-terminus is directed toward the cytosol. We also demonstrated that SLC35A5 formed homomers, as well as heteromers with other members of the SLC35A protein subfamily. In conclusion, the SLC35A5 protein might be a Golgi-resident multiprotein complex member engaged in nucleotide sugar transport.

Our previous results suggested that EPS11, a novel marine bacterial polysaccharide, might be a potential drug candidate for human non-small cell lung carcinoma treatment. In this study, we further investigate the anticancer mechanisms against liver cancer and the anti-metastatic effects in vivo of EPS11. Firstly, we found that EPS11 exerts cytotoxic effects via blocking cell adhesion and destroying filiform structure formation in Huh7.5 cells. Moreover, mass spectrometry-based proteomic analysis of EPS11-treated Huh7.5 cells revealed that expression of many adhesion-related proteins was significantly changed. It is noteworthy that the expression of CD99, a key factor related to cell adhesion, migration and cell death, is remarkably down-regulated after EPS11 treatment. Importantly, over-expression of CD99 partly rescues cell death rate, and improves cell adhesion and migration ability in Huh7.5 treated by EPS11. Thus, we propose that CD99 is a potential action target of EPS11, inhibiting cancer cell proliferation, adhesion and migration. Notably, administration of EPS11 simultaneously with tumor induction evidently reduces tumor nodule formation in the lungs, which strongly indicates that EPS11 has anti-metastatic effects in vivo. Taken together, our results suggest that EPS11 inhibits liver cancer cell growth via blocking cell adhesion and attenuating filiform structure formation, and has potential as an anti-cancer drug, targeting metastasis of cancer cells, in the future.

'Biased' ligands of G protein-coupled receptors (GPCRs) represent a type of promising analgesic with reduced on-target side effects. PZM21, a potent μ-opioid-receptor (μOR)-biased agonist with a new chemical scaffold compared to classic opioids, has been identified as a therapeutic lead molecule for treating pain. In the current study, novel PZM21 analogues were synthesized and evaluated for their in vitro and in vivo efficacy. Novel compound 7a and PZM21 demonstrated undetectable β-arrestin-2 recruitment, however, their analgesic effects need to be further confirmed. Compounds 7b, 7d, and 7g were stronger analgesics than PZM21 in both the mouse formalin injection assay and the writhing test. Compound 7d was the most potent analogue, requiring a dose that was 1/16th to 1/4th of that of PZM21 for its analgesic activity in the two assays, respectively. Therefore, compound 7d could serve as a lead to develop new biased μOR agonists for treating pain.

Magnolia zenii is a critically endangered species known from only 18 trees that survive on Baohua Mountain in Jiangsu province, China. Little information is available regarding its molecular biology, with no genomic study performed on M. zenii until now. We determined the complete plastid genome of M. zenii and identified microsatellites. Whole sequence alignment and phylogenetic analysis using BI and ML methods were also conducted. The plastome of M. zenii was 160,048 bp long with 39.2% GC content and included a pair of inverted repeats (IRs) of 26,596 bp that separated a large single-copy (LSC) region of 88,098 bp and a small single-copy (SSC) region of 18,757 bp. One hundred thirty genes were identified, of which 79 were protein-coding genes, 37 were transfer RNAs, and eight were ribosomal RNAs. Thirty seven simple sequence repeats (SSRs) were also identified. Comparative analyses of genome structure and sequence data of closely-related species revealed five mutation hotspots, useful for future phylogenetic research. Magnolia zenii was placed as sister to M. biondii with strong support in all analyses. Overall, this study providing M. zenii genomic resources will be beneficial for the evolutionary study and phylogenetic reconstruction of Magnoliaceae.

: The stability profile of a new 1,4-dihydropyridine derivative (DHP), representative of a series with a hexahydroquinoline ring, was studied to design light-stable liquid formulations. This molecule, named M3, has been shown among the analogs to have a high capacity to block both L- and T-type calcium channels. The ethanol solution of the drug was subjected to a photodegradation test, in accordance with standard rules. The concentrations of the drug and its byproducts were estimated using multivariate curve resolution, applied to the spectral data collected during the test. The improvement of both the photostability and water solubility of M3 was investigated by adding the surfactant polysorbate 20 in a 1:5 ratio to aqueous solutions of the drug. These formulations were exposed to stressing light in containers of bleu polyethylene terephthalate (PET), amber PET, and covered amber PET. The best results were obtained when using the covered amber PET container, reaching a degradation percentage of the drug less than 5% after 12 h under an irradiance power of 450 W/m². The stability of the compound was compared to that of nimodipine (NIM) under the same conditions.

Seaweed powder has been found to act as an effective catalyst for the fixation of CO₂ into epoxides to generate cyclic carbonates under solvent free conditions. Model background reactions were performed using metal halides and amino acids typically found in common seaweeds which showed potassium iodide (KI) to be the most active. The efficacy of the seaweed catalysts kelp (Laminaria digitata) and dulse (Palmaria palmata) was probed based on particle size, showing that kelp possessed greater catalytic ability, achieving a maximum conversion and selectivity of 63.7% to styrene carbonate using a kelp loading of 80% by weight with respect to epoxide, 40 bar of CO₂, 120 °C for 3 h. Maximizing selectivity was difficult due to the generation of diol side product from residual H₂O found in kelp, along with a chlorinated by-product thought to form due to a high quantity of chloride salts in the seaweeds. Data showed there was loss of organic matter upon use of the kelp catalyst, likely due to the breakdown of organic compounds and their subsequent removal during product extraction. This was highlighted as the likely cause of loss of catalytic activity upon reuse of the Kelp catalyst.

In this paper, a monitoring system of agricultural production is modeled as a Data Fusion System (data from local fairs and meteorological data). The proposal considers the particular information of sales in agricultural markets for knowledge extraction about the associations among them. This association knowledge is employed to improve predictions of sales using a spatial prediction technique, as shown with data collected from local markets of the Andean region of Ecuador. The commercial activity in these markets uses Alternative Marketing Circuits (CIALCO). This market platform establishes a direct relationship between producer and consumer prices and promotes direct commercial interaction among family groups. The problem is presented first as a general fusion problem with a network of spatially distributed heterogeneous data sources, and is then applied to the prediction of products sales based on association rules mined in available sales data. First, transactional data is used as the base to extract the best association rules between products sold in different local markets, knowledge that allows the system to gain a significant improvement in prediction accuracy in the spatial region considered.

Taste is influenced by several factors. However, whether habitual exercise level is associated with differences in taste perception has received little investigation. The aim of this study was to determine if habitual exercise is associated with differences in taste perception in men. Active (n = 16) and inactive (n = 14) males, between ages 18⁻55, underwent two days of sensory testing, using prototypical taste stimuli of high and low concentrations for sweet, salt, bitter, sour, umami, and carbohydrate (maltodextrin). Mean perceived intensity and hedonic ratings were recorded. Eating behaviour was assessed by the three factor eating questionnaire and food intake by EPIC food frequency questionnaire (FFQ). There were moderate to large differences between the two groups in perceived intensity for sweet taste at the high concentration and umami taste at both high and low concentrations, with active males recording a higher perceived intensity (p < 0.05 for all). The active group also recorded a greater dislike for umami low and carbohydrate low concentration (p < 0.01). Salt, bitter and sour perception did not significantly differ between the two groups. FFQ analysis showed no difference in % energy from macronutrients between the groups. Eating behaviour traits correlated with sweet taste intensity and umami taste liking, independent of activity status. Results indicated that sweet and umami taste perception differ in active compared to inactive males. Habitual exercise level should be considered in taste perception research and in product development. Whether differences in taste perception could be one factor influencing food intake and thus energy balance with habitual exercise warrants further investigation.